Pittsburgh at Cleveland, 1 p.m. ET, CBS: Cleveland has won two of the last 43 games, failing to come out ahead in 17 straight contests. The Browns were actually favored once last year and were an underdog of only three points or fewer three other times, but this number is still lower than one would normally expect. Is there a “Hard Knocks” influence in this line? Cleveland has been favored in all four preseason games, winning three outright. Top pick Baker Mayfield will sit behind Tyrod Taylor, who will have Josh Gordon at his disposal. The talented receiver won’t start but should factor in substantially behind Jarvis Landry and rookie Antonio Callaway. Coming off a well-publicized suspension, he’s overcome a hamstring issue that kept him from practicing much this preseason. Carlos Hyde and Nick Chubb should make for a formidable running back tandem, so we’ll see if Todd Haley can secure immediate dividends as offensive coordinator of his new group against a defense he faced daily in practice for the last six seasons.
The Pittsburgh offense will have to solve a defense that has looked fantastic under Gregg Williams, who has no problem blitzing teams in the preseason when others take a more vanilla approach. Former No. 1 pick Myles Garrett has looked tremendous and others have had an excellent run leading up to this season opener, but it remains to be seen what effect cutting LB Mychal Kendricks will have after he was charged with insider training. The Steelers will be without Le’Veon Bell, who hadn’t reported to the team as of Friday due to a contract dispute. James Conner, a second-year back out of Pitt who ran for just 144 yards as a rookie will start in Bell’s place. Antonio Brown will be out there as Ben Roethlisberger’s top target despite dealing with a quad issue while veteran guard Ramon Foster has also been upgraded to probable after dealing with a knee injury. After calling out Bell, the offensive line is expected to try and ball out for Conner, so we’ll see how they fare against an improved Cleveland pass rush. The Browns haven’t won a season opener since 2004 and are 3-14 against the number in the last 17 meetings against the Steelers in Cleveland and are 1-9 straight up in their last 10, part of a run that has seen them prevail in only four of 35 encounters with their AFC North rival since 2001. Meanwhile, Pittsburgh has won its last 10 divisional games.
San Francisco at Minnesota, 1 p.m. ET, FOX: 49ers QB Jimmy Garoppolo won all five of his starts last season but faces his biggest test with one of the NFL’s top defenses getting the past month-plus to prepare for him with plenty of tape to study. We’ll see what tendencies the Vikings can identify and potentially exploit and will have CB Xavier Rhodes (hamstring) in the mix and rookie Mike Hughes in a heightened role since Mackensie Alexander is listed as doubtful. The Vikes won’t have to deal with former teammate Jerick McKinnon, who signed on in the offseason but tore his ACL, leaving all the carries to veteran Alfred Morris and second-year back Matt Breida.
Minnesota upgraded its quarterback by handing Kirk Cousins a massive contract and also welcomes Dalvin Cook back from injury, so we’ll see how the offense takes shape. Adam Thielen has been cleared after rolling his left ankle last week, so the major question mark for the Vikings’ offense comes up front since center Pat Eflein has been ruled out and Nick Easton was lost for the season with a neck injury. Brett Jones will start. The 49ers will be without top linebacker Reuben Foster, who is serving a two-game suspension. Arik Armstead will be out there despite a hamstring issue and will be out there trying to wreak havoc along the defensive line with fellow first-round picks Solomon Thomas and DeForest Buckner. San Francisco has lost its last five games in Minnesota. The Vikings have won their last six home games and are 13-4 at U.S. Bank Stadium. The ‘under’ is 5-1 in the last six meetings between these two.
Cincinnati at Indianapolis, 1 p.m. ET, CBS: After squaring off in the preseason finale, these neighbors kick off the season with Andrew Luck’s return taking center stage. After missing all of 2017, he will face an aggressive defense that will be missing their leader with Vontaze Burfict suspended for the first four games. Luck participated in the preseason but the Colts put very little on display and will be working with a young offensive line that requires No. 6 pick Quenton Nelson to perform well immediately. The run game is also a question mark with mainstay Frank Gore gone and Marlon Mack questionable with a hamstring issue. Tackle Anthony Castonzo (hamstring) should play but Denzelle Good won’t, so conditions aren’t exactly ideal for Luck to feel like he’ll be protected in his first regular-season game in 20 months.
The Bengals have a new defensive coordinator in the very competent Teryl Austin, but this group has seen their level diminish without Burfict in the past. We’ll see how Austin compensates. Andy Dalton will start his eighth consecutive season opener for Cincy and will again have A.J. Green, but the passing game finally gets deep threat John Ross out there after he missed most of his rookie season with knee and shoulder issues after fumbling on his first snap. Tight end Tyler Eifert has also returned from a back issue, so we’ll see the offense at full strength in Bill Lazor’s second season as the coordinator. Indianapolis has won eight of 11 against the Bengals.
Buffalo at Baltimore, 1 p.m. ET, CBS: A.J. McCarron was traded and Josh Allen was beaten out for the starting gig by Nathan Peterman, whose rookie season was marred by throwing interceptions every time he tried to get something accomplished. LeSean McCoy wasn’t suspended for his offseason drama and WR Kelvin Benjamin has had an entire preseason with his new team. New coordinator Brian Daboll will match wits with Don Martindale, the long-time linebackers coach who is taking over the defense from Dean Pees. He’ll have to make up for the absence of Jimmy Smith (suspension), but has a unit that returns almost everyone and actually stayed healthy throughout camp.
Lamar Jackson should debut in some capacity since the Ravens have been experimenting with packages that can take advantage of his speed and elusiveness. Joe Flacco took to the increased competition from the rookie first-round pick and Robert Griffin III and had his sharpest camp in years, developing chemistry with new receiving weapons Michael Crabtree, John Brown and Willie Snead. Flacco’s 141.4 passer rating topped all NFL quarterbacks in the preseason. It’s expected to rain most of the weekend in the Baltimore area, so be sure to check the forecast before placing a wager here. Buffalo has dropped four straight at the Big Crabcake and has only won three of its last 11 road games.
Jacksonville at N.Y. Giants, 1 p.m. ET, FOX: New York opened last season as a Super Bowl contender before Odell Beckham, Jr. was injured and the bottom fell out on the Ben McAdoo era. Pat Shurmur, who has run the offense for Minnesota and Philadelphia over the past few years, will team with Mike Shula to get the most out of an offense set to debut No. 2 pick Saquon Barkley at running back in order to take pressure off 15-year veteran Eli Manning. Barkley has been dealing with a hamstring issue and tight end Evan Engram has come through concussion protocol, but the Giants are still thin at tackle and may have issues blocking against one of the NFL’s top defenses. Beckham’s duel with standout Jags corner Jalen Ramsey will get the most attention, but there are other crititcal matchups that could decide this one.
New York must find a way to harass Blake Bortles into turnovers despite missing Olivier Vernon, who was expected to be a standout in a new look 3-4. Rookie Lorenzo Carter, a third-round pick out of Georgia, will be cast in a huge role as a result. The Jags will rely on a slimmer Leonard Fournette to try and slow down New York’s pass rush and will likely utilize a heavy dose of the ground game due to potential showers being part of the forecast. Jacksonville has gone 5-1 against the number in its last six games against the Giants but will need new receivers to step up against a secondary that on paper, appears to be the strength of the defense. We’ll see if young options like Dede Westbrook and rookie DJ Chark can rise up to keep the Jags from being one-dimensional.
Tampa Bay at New Orleans, 1 p.m. ET, FOX: The week’s biggest favorite saw their advantage grow when final injury reports were released on Friday since it appears that top corner Brent Grimes will be unable to shake off a groin injury in order to play. With backup De’Vante Harris (hamstring) also doubtful, the Bucs will be thin and young at corner going on the road against a quarterback that doesn’t need help taking healthy secondaries apart. Rookies Carlton Davis and M.J. Stewart will play large roles and face a baptism by fire. First-round pick Vita Vea hasn’t played due to a calf injury, so the Bucs won’t have the No. 12 pick who they envisioned being disruptive. The Saints will be missing RB Mark Ingram to a four-game suspension but should have starting guard Andrus Peat (guard) in the mix up front to help block for Brees and open holes for Alvin Kamara.
With Jameis Winston suspended for the first three games of the season, it will be on Ryan Fitzpatrick to try to help Tampa Bay’s offense keep pace with the Saints. The 14-year veteran will lean on Mike Evans, who has a checkered history with corner Marshon Lattimore, so keep an eye on that matchup. The Bucs saw No. 38 pick Ronald Jones (USC) gain just 22 yards on 28 preseason carries, dampening enthusiasm over his addition and solidifying Peyton Barber as the starter. Tampa Bay has lost its last seven games as a road underdog but New Orleans have won only one of its last 10 September games. That includes an 0-4 record SU and ATS at home in the Superdome. The Saints have won 10 of 13 in this series since Nov. 2011.
Houston at New England, 1 p.m. ET, CBS: Tom Brady vs. Deshaun Watson to start the season provides an awfully juicy matchup pairing the game’s top quarterback against one of the most promising young prospects and potential heirs to the throne. Last year’s contest produced a 36-33 The contrast in their styles adds to the entertainment value, especially since Brady will have to deal with a healthy J.J. Watt, Whitney Mercilus and Jadeveon Clowney on the hunt as he tries to work. He may not have left tackle Marcus Cannon available to help keep his uniform clean, although the calf injury that kept him out this preseason has healed enough for him to participate in practices this week. Brady probably won’t have rookie RB Sony Michel in the mix but will otherwise have a loaded arsenal of weapons that includes new toys like Jeremy Hill and Cordarrelle Patterson in addition to Rob Gronkowski, James White, Rex Burkhead Chris Hogan and Phillip Dorsett. The Texans will have starting corner Kevin Johnson available after he cleared concussion protocol, but veteran Kayvon Webster, signed to a one-year deal to improve depth, isn’t ready to contribute yet. Safety Andre Hal and rookie corner Jermain Kelly are out.
Bill Belichick has Josh McDaniels back to run the offense after he reneged on Indianapolis’ head coaching job but will be breaking in a new defensive coordinator with Brian Flores running plays. Houston’s Bill O’Brien is expected to hold back little with Deshaun Watson at 100 percent and will look to make the Patriots work by ensuring his quarterback takes advantage of his opportunities to run. Watson threw for 301 yards against New England last season and ran for another 41 against a defense that has had its issues early in seasons of late. Watson’s chances of lighting up the Pats again would improve if Will Fuller is able to be a factor. He’s a game-time decision due to a hamstring injury. The Texans have lost seven straight in this series and have won only once in 10 career meetings.
Tennessee at Miami, 1 p.m. ET, FOX: Ryan Tannehill’s ill-timed ACL tear sabotaged Miami last season, forcing them to turn to Jay Cutler. He took part in preseason action, throwing for a score while not committing a turnover, but this is going to be a major test right out of the box. Tennessee will have an aggressive defensive game plan in place with head coach Mike Vrabel and veteran coordinator Dean Pees joining forces. The Dolphins are hoping that Kenyan Drake can emerge as a workhorse and have veteran Frank Gore and rookie Kalen Ballage on board, so we might see a major emphasis on the ground game in this one in order to ease Tannehill in and survive the absence of top WR DeVante Parker, who is sitting with a finger injury. Danny Amendola should factor in heavily in his debut. Tennessee got bad news with safety Kendrick Lewis (foot) and rookie LBs Rashaan Evans and Harold Landry ruled out. The secondary already lost safety Jonathan Cyprien for the season early in camp. DE Derrick Morgan will play.
Titans tight end Delanie Walker, Marcus Mariota’s security blanket, is going to play after sitting out the preseason to rest his toe. The Dolphins struggled to cover that position well last season, so Walker and FIU product Jonnu Smith could feature prominently. The offensive line will be without starting tackle Jack Conklin, so they’ll be relying on veteran backup Dennis Kelly to help create space for Mariota, Derrick Henry and newcomer Dion Lewis, who should provide a versatile threat out of the backfield. Tennessee went winless and didn’t cover this preseason so the team is looking for its first taste of success under the new leadership. Thunderstorms are a possibility in South Florida but likely won’t factor in until late in the game if at all.
Kansas City at L.A. Chargers, 4:05 p.m. ET, CBS: Patrick Mahomes II won his first start last season in a meaningless Week 17 game, so he’s got that experience to draw on as he takes over as Kansas City’s starting quarterback. That victory came in Denver, so he’s performed on the road and won’t have to deal with much of an atmosphere in Carson since the StubHub Center offers the Chargers the least significant homefield edge in the NFL. Mahomes also won’t have to deal with top Chargers pass rusher Joey Bosa, who will miss the game with a foot injury. Corey Liuget is serving a four-game suspension and the secondary has already lost a few key bodies, so a few factors have lineup in his favor as he looks to build on the success Alex Smith enjoyed. The presumption is that the Chiefs may take a step back due to his inexperience and proclivity for mistakes, but the arm talent he brings to the table could help push weapons like Travis Kelce, Sammy Watkins and Tyreek Hill to another level.
Philip Rivers has plenty of help to try and put the Chargers over the top following a frustrating season that saw his team go 1-4 in games decided by three or fewer points. With Keenan Allen and Mike Williams available in addition to Tyrell Williams and RB Melvin Gordon, L.A. should be able to put up points against a secondary that struggled last season and traded Marcus Peters to the Rams. He picked off Rivers twice in the last meeting between these teams. Starting safety Daniel Sorensen is out with a knee injury and veteran Eric Berry is doubtful due to a heel issue. Those absences put Kansas City’s streak of eight consecutive victories against their AFC West rival in jeopardy. The Chiefs have won 16 of 17 within the division under Andy Reid.
Seattle at Denver, 4:25 p.m. ET, FOX: Case Keenum will attempt to solidify the quarterback position for Denver, which has gone 14-18 since winning Super Bowl 50. Paxton Lynch is unemployed, Trevor Siemian is a backup in Minnesota and Brock Osweiler is doing the same in Miami, so all the bad men are gone. Although C.J. Anderson and Aqib Talib will be missed, a younger determined group will look to keep Vance Joseph off the chopping block, which will likely hinge on a strong start to the season. Rookie Royce Freeman will start ahead of Devontae Booker, while Adam Jones is going to start in Talib’s spot and probably return punts after asking for Champ Bailey’s number in an attempt to “honor” his legacy. Denver lost each of its preseason home games but won the last two, looking impressive in a dress rehearsal win at the Redskins.
Seattle is reloading on the run, moving on from the Legion of Boom era but still clinging to one key component with Earl Thomas ending his holdout. He’s returned to practices and is considered a game-time decision in this season opener but will likely play. Rookie Shaquem Griffin has been announced as a starter for a new-look defense that saw Kam Chancellor retire, LB K.J. Wright and DE Dion Jordan ruled out due to injuries and numerous other contributors like Richard Sherman, Michael Bennett, Sheldon Richardson and Cliff Avril no longer around. Ken Norton, Jr., who didn’t have much success as a defensive coordinator in Oakland, takes over those duties this season. It remains to be seen if new offensive coordinator Brian Schottenheimer opens things up for Russell Wilson given the uncertainty surrounding the defense, but that hasn’t been his history. Top target Doug Baldwin (knee) and rookie running back Rashaad Penny (finger) will both be available. The Seahawks have dropped their last six September road games, failing to cover any of them. Conversely, Denver is 8-1 SU (7-1-1 ATS) at home over the last few years in the season’s opening month and has won 17 of 24 against the Seahawks.
Dallas at Carolina, 4:25 p.m. ET, FOX: Over the past few seasons, Dallas’ strength has been an offensive line that has created opportunities for Tony Romo and Dak Prescott while giving Ezekiel Elliott a lot of room to work. As the 2018 season begins, that advantage appears to have diminished. Center Travis Frederick is out with Guillain-Barre syndrome, experiencing numbness in his feet, hands and arms. Replacement Joe Looney has never started at center. Rookie Connor Williams will start at left guard with Chaz Green no longer around. Zack Martin will be available but has been struggling with a knee injury. With Dez Bryant gone, Prescott will have to make the aerial attack work with Tavon Austin, Allen Hurns and rookie Michael Gallup. Can tight end Rico Gathers take the next step in his development?
The Panthers will go as far as Cam Newton takes them, but he’s got offensive line issues of his own to contend with. They’ll be looking to execute a new offense with veteran Norv Turner at the helm, going up against a familiar face in good friend Jason Garrett and his one-time former employer. Left tackle Matt Kalil is on IR, while right tackle Daryl Williams is questionable after tearing his MCL and dislocating his patella back in the team’s first practice. Guard Amini Silatolu is also questionable with a knee issue. The addition of C.J. Anderson, Torrey Smith and rookie WR DJ Moore give Newton help, while Christian McCaffrey sowed off increased explosiveness in the preseason. Carolina has won 24 of its last 30 in Charlotte, where thunderstorms may be a part of the equation late Sunday afternoon.
Washington at Arizona, 4:25 p.m. ET, FOX: Arizona begins the Steve Wilks era against visiting Washington, turning the keys over to newcomer Sam Bradford, who will play mentor to top pick Josh Rosen until the time is right to pass the torch. Or until he gets hurt, which let’s face it, is a strong possibility since he hasn’t played all 16 games of a season since 2012. He was the NFC Offensive Player of the Week for his performance in last year’s season opener, a Monday night home win over New Orleans, and had a solid preseason. David Johnson is returning from a wrist injury that cost him most of 2017, but center AQ Shipley already landed on IR, complicating matters since the ‘Skins arrive with an aggressive defense that can do a lot of damage with Alabama products Jonathan Allen and Daron Payne up front.
Alex Smith will make his first start with his new team, likely with Adrian Peterson lined up behind him on his first snap from scrimmage. Few could’ve seen that coming. Rookie second-round pick Derrius Guice tore his ACL in early August, so Peterson was signed to try and handle some of the workload with versatile back Chris Thompson also due to see extensive action. Tight ends Jordan Reed and Vernon Davis are also expected to see major roles as the offense takes on a new personality after Kirk Cousins moved along. Washington has won nine of 11 against the Cardinals.
Chicago at Green Bay, 8:20 p.m. ET, NBC: Chicago will have LBs Khalil Mack and Roquan Smith in the lineup but both are likely to be on a pitch count due to a lack of preparation time with the Bears and veteran coordinator Vic Fangio. Leonard Floyd (hand) is also expected to play, so the Packers and their opposition going forward will have to contend with a special group once everyone gets settled. Green Bay is fortunate in that it gets to host this game and face this defense before they’ve had a chance to truly come together, so Aaron Rodgers has an opportunity to start strong. He’ll have tackles Bryan Bulaga (knee) and David Bakhtiari (ankle) in the mix in front of him and his entire receiving corps available despite losing Jordy Nelson.
The Bears are looking for growth from second-year QB Mitch Trubisky, who has himself two potential No. 1 receivers in newcomer Allen Robinson and rookie Anthony Miller out of Memphis. The 51st pick was fantastic in the preseason and could quickly emerge next to the former Jaguars standout, while Josh Bellamy and Taylor Gabriel are also on board alongside versatile tight end Trey Burton and backs Jordan Howard and Tarik Cohen. The ingredients are there for first-year head coach Matt Nagy to put together a quick turnaround. Chicago has dropped nine consecutive games against NFC North competition and runs into a Green Bay squad that has won 16 of its last 19 September home games (13-5-1 ATS) and is 16-3 SU against the Bears since 2009, scoring 20 or more points in only six of those 19 contests. Conditions at Lambeau should be cool on a crisp, clear night where temperatures will dip into the low 50s.