Colts at Titans (-3/43), 1 p.m. ET, CBS: Jacoby Brissett had an excellent first outing in his now full-time role as Colts quarterback, putting some great throws in getting to overtime against the Chargers. L.A. had some key defensive personnel out and doesn’t offer much of a homefield advantage, so this divisional matchup with the Titans should offer a much tougher test. Indianapolis is looking for a better effort from top linebacker Darius Leonard after a rough outing in Carson, so his encounters with Tennessee star Derrick Henry will play a large role. Henry averaged over five yards per carry against Indy last season but got only 26 touches – one receiving target – in his team’s two losses.
The Colts will be without speed rusher Kemoko Turay (neck), who was disruptive last Sunday. Tennessee is still working with a patchwork offensive line due to tackle Taylor Lewan’s suspension and guard Kevin Pamphile’s knee injury, but that didn’t stop it from a big day in Cleveland and isn’t expected to be an issue here. Indianapolis has won 13 of 15 in the series but has dropped two of the past three against the Titans. To pull off an upset, the Colts will need another big game from RB Marlon Mack (174 yards in Week 1) and WR TY Hilton, who has had plenty of productive outings against Tennessee over the years. Temperatures on the field will be right around 100 degrees, so the better conditioned team should have the advantage come second half.
Chargers (-1.5/47.5) at Lions, 1 p.m. ET, CBS: After surviving the Colts, the Chargers hit the road as a slight favorite despite a number of key injuries. By now you know RB Melvin Gordon is holding out, top tackle Russell Okung is on IR until at least week 6 and safety Derwin James is missing substantial time. Tight end Hunter Henry (knee) and a pair of key corners, Michael Davis (hamstring) and Trevor Williams (quad) won’t play against Detroit, while WR Mike Williams (knee) and linebackers Jatavis Brown and Denzel Perryman will be game-time decisions. Despite all the attrition, L.A. is making and expects to continue a run that has seen them win nine of 10 games away from their “home” environment in Carson. RBs Austin Ekeler and Justin Jackson will join top target Keenan Allen as Philip Rivers best options to try and secure another road win, while the Lions will be hoping to put blowing a massive lead and winding up tied with Arizona in the rear-view.
Lions tackle Taylor Decker (back) hasn’t been able to do much and could miss the game after struggling at left tackle against the Cardinals. Top linebacker Jarrad Davis (leg) is hoping to return, while DT De’Shawn Hand (elbow) and corner Rashaan Melvin (knee) are likely out. Top CB Darius Slay will need to help bottle up Allen to encourage Rivers to look elsewhere, so that will be this contest’s most telling matchup. Matthew Stafford had an excellent debut before losing his rhythm as the Lions tried to kill clock in Glendale, but he established instant chemistry with top pick T.J. Hockenson as the rookie tight end, who set a positional NFL record for most yards in a debut with his 124. Lions fans are hoping to be treated to a similar performance and a happier ending despite their team being a home ‘dog. The Chargers have won seven of eight meetings between these teams since 1981, only losing in their last trip into Ford Field back in 2011.
Bills (-2/44.5) at Giants, 1 p.m. ET, CBS: The Bills looked lost, down 16-0 against the Jets late in the third, before LB C.J. Mosley exited and the offense finally hit their strides, scoring 17 points on three straight drives in a run punctuated by a blown coverage on a jump ball Josh Allen was fortunate to complete. The offense is young and figures to be that streaky, but the defense supplied many reasons to be hopeful that this group will be able to compete for a playoff spot. The unit is undoubtedly the reason Buffalo is favored on the road for the first time since Dec. 31, 2017, making this only the second occasion in 13 regular-season games that the Bills are laying points outside upstate New York. They’ll have a regularly healthy squad since WR Cole Beasley has been cleared to play after dealing with an illness, so only WR/KR Andre Roberts and CB Taron Johnson have been ruled out.
New York got off to a nice start against Dallas and then imploded, so the boo birds will file into MetLife Stadium cocked and ready to go if they don’t like what they see. Giants fans want to see rookie Daniel Jones but know its too early in the season to turn on Eli Manning, so he’ll have a grace period of sorts before they turn on him. Saquon Barkley rushed for 120 yards on 11 carries against the Cowboys and should see a much heavier workload considering Buffalo was the top pass defense in the league last season but was stuck in the middle against the run. Sterling Shepard is out due to a concussion, so New York is down to Bennie Fowler, Russell Shepard and Cody Core as receiving targets they can be sure will be healthy enough to play. Evan Engram will be Manning’s first option, but he’ll need one or two of his receivers to come through if the Giants are going to pull off a win to beat Buffalo for the fifth time in six tries since 1999. The Bills’ lone victory came in East Rutherford in 2003.
Cardinals at Ravens (-13/46), 1 p.m. ET, FOX: There are a number of folks on the Cardinals here, hopping on the second-largest spread of Week 2 in hopes that the line is partially an overreaction to what Baltimore was able to do to in South Florida in hanging 59 points on the Dolphins. They’re not going to be able to carry any of those touchdowns over but have an opportunity to continue partying in the end zone if Lamar Jackson’s pocket prowess continues. John Harbaugh has been terrific early in the season throughout the course of his career and has excelled in home openers, while Jackson’s confidence shone through against a Dolphins secondary that is one of the strengths of that tanking, depleted group. Arizona remains without Patrick Peterson due to suspension but did pack Ravens legend Terrell Suggs, who returns to Baltimore on the heels of two sacks in his new team’s Week 1 tie.
Kyler Murray will look to build on finally finding a rhythm against Detroit in leading a fourth-quarter comeback after really looking like an overmatched rookie through the first three quarters. He’ll now also have to deal with a road atmosphere and a veteran defense. Corner Jimmy Smith hurt his knee in Miami and has been ruled out but the rest of the group is good to go since fellow corner Marlon Humphrey was cleared after a back issue. The Cardinals will hope to establish the run and screen game through David Johnson to keep the pressure off Murray but will likely need to hit a few home runs to have a chance to steal this late. The Ravens have won four of the last five meetings between these teams but dropped the most recent one, falling in Glendale in ’15.
Patriots (-18.5/48.5) at Dolphins, 1 p.m. ET, CBS: The Patriots are the largest road favorite in 32 years, opening at 17.5 and steadily climbing. Antonio Brown hasn’t been placed on the commissioner’s exempt list and is therefore available to play if Bill Belichick wants to utilize him. All signs point to him debuting in his newest uniform in his backyard, so you can expect the South Florida native to want to make a splash. Despite the uneven preseason, he should be physically ready to have a massive impact. Josh Gordon shined in Week 1 alongside Philip Dorsett, a Ft. Lauderdale native who will also be tripping over his cleats to get over in front of friends and family. At this point, the Dolphins are nothing more than a punching bag or speed bump.
New starting tackle Julien Davenport, safety Reshad Jones and speedy receiver Albert Wilson have already been ruled out due to injuries, so a patchwork offensive line will be in play for Miami. Defensively, while prized DB Minkah Fitzpatrick will likely get his wish to be traded, he’s expected to be out there for this one. The Patriots have covered only one of their last six in South Florida, which combined with such a large number, should be able to pick up some action for Ryan Fitzpatrick and the ‘Phins. If you’re taking the points, just beware that it’s too early in the season for Tom Brady to be disinterested, especially with so many new toys. Baltimore racked up 643 yards and scored six offensive touchdowns by halftime, so if the Dolphins don’t show up ready to play, another embarrassment awaits. Thunderstorms could factor in, so if there’s lightning in the area, we might see stoppages.
Cowboys (-5.5/46.5) at Redskins, 1 p.m. ET, FOX: Jerry Jones has to be thrilled that he relented and paid Ezekiel Elliott his money since it looks like he’s about to have a lot of fun. Zeke largely played decoy as Amari Cooper, Michael Gallup and Randall Cobb torched the Giants secondary as Dak Prescott dominated with his ball placement and decision-making. It’s not going to look that easy every week, but the Cowboys will try their best to replicate that effort in Landover. The Redskins lost their top defensive player with Jonathan Allen suffering an MCL tear and have issues in the secondary with Quinton Dunbar (knee) and Fabian Moreau (ankle) likely sidelined.
Washington will turn to Adrian Peterson after losing Derrius Guice to a knee injury and won’t have tight end Jordan Reed due to a concussion. Offensive tackle Trent Willliams is still a holdout, but none of this prevented the Redskins from securing a backdoor cover with six seconds left in Philly after blowing a 17-0 lead. Case Keenum had a productive day and rookie WR Terry McLaurin impressed, so those two will have to hook up for huge days if there’s going to be a surprise here.
Jaguars at Texans (-8/43), 1 p.m. ET, CBS: Rookie Gardner Minshew got the bulk of the work in the preseason and often couldn’t generate much offense. He was working behind a backup offensive line with receivers who for the most part didn’t stick, but it was nonetheless stunning that he performed a complete 180 in taking over when Nick Foles broke his collarbone. Minshew set an NFL record for accuracy by completing 22 of 25 passes and made good on his first 13, adjusting immediately to the speed of the game. We’ll see how he fares on the road against an angry Texans defense that allowed itself to get clipped at the end by a 58-yard Will Lutz field goal on Monday night. J.J. Watt had a quiet evening and Drew Brees was able to get his playmakers the ball without much hassle, so Romeo Crennel’s group will look to atone here against a division rival’s rookie-led offense.
Although Deshaun Watson put Houston in position to win with clutch throws and Kenny Stills made an immediate impact, the Texans’ offensive line played terribly in allowing Watson to spend significant time on his back and running for his life. The Jags will get after him too, so new tackle Laremy Tunsil needs to bounce back with his pass protection while emerging as a game-changing force on screens. Speaking of which, slot receiver Keke Coutee is expected to return. Jacksonville’s defense will be missing DE Yannick Ngakoue and corner A.J. Bouye.
Seahawks at Steelers (-3.5/47), 1 p.m. ET, FOX: Ben Roethlisberger had an awful debut against the Patriots, watching his streak of consecutive games with a touchdown pass end at 26. He didn’t look sharp, so facing an aggressive Seattle secondary will be a test, although it appears that he’s going to catch a break due to injuries. Seahawks safety Tedric Thompson (hamstring), DT Poona Ford (calf), DE Ziggy Ansah (shoulder) and CB/special teams captain Neiko Thorpe are all expected to miss this contest. With Juju Smith-Schuster cleared to play after a toe issue and center Maurkice Pouncey back to anchor the offensive line, the Steelers will at least be better equipped to help Roethlisberger bounce back. No matter how early it is, it wouldn’t be great for Pittsburgh to open 0-2 at home given the projected improvement of both the Ravens and Browns. This is an early must-win and should feature the return of safety Sean Davis (ankle) and possibly CB Joe Haden (shoulder).
The Seahawks will rely on Russell Wilson to lead a young offense on the road. Seattle went 4-4 SU last season but were in most games. Outside of two blowout wins, the Seahawks played six road games decided by a touchdown or fewer. They’ve been slow starters and have gone 1-6-1 ATS over the last few seasons in September. The Seahawks won the most recent meeting between these teams in 2015 but have been shut out on their last two trips to Pittsburgh.
49ers at Bengals (-1/46), 1 p.m. ET, FOX: The 49ers rode a pair of pick-sixes past Tampa Bay last week and are back on the road hoping to start the season with consecutive wins despite Jimmy Garoppolo still working his back into a rhythm. He looked better against the Bucs than he did in the preseason and in practices, but did throw a pick-six of his own and can be harassed into mistakes. He does know how to get George Kittle the ball, which may make the difference here given Cincinnati’s new-look linebacker corps that also have to deal with Matt Breida, who is good to go as the starter.
Cincinnati has yet to clear RB Joe Mixon after he injured an ankle in Seattle but him being able to practice some late in the week is a good sign he’ll at least try to play in this home opener. Andy Dalton will look to prove he can make plays without A.J. Green commanding attention, but has to deal with a secondary that will see Jason Verrett make his 49ers debut and could also feature Jimmie Ward’s return from a hand injury. The Bengals could be without Mixon, Green and top tackle Cordy Glenn, who has been ruled out with a concussion.
Vikings at Packers (-2.5/43), 1 p.m. ET, FOX: With both teams coming off victories, the NFC North will have an early leader setting the pace after this one. Matt LaFleur’s debut as head coach against the Bears came courtesy of a tremendous defensive effort and put Aaron Rodgers’ lack of comfort with the new offense on display. There should be progress in Week 2 at home considering David Bakhtiari and Bryan Buluaga are healthy enough to anchor the line and buy time for Rodgers to work his magic. The Packers play five of their next six at Lambeau Field and lived to tell about a rough night in Chicago to open the season, boosting team morale in that Rodgers was able to give LaFleur the game ball for his first win without any hint of sarcasm. Things are good in Packerland. We’ll see if that continues after the Vikings leave town.
Minnesota head coach Mike Zimmer and his defense is one reason Mike McCarthy had to move on since they’ve emerged as a major thorn in Rodgers’ side. The Vikes are 5-1-1 over the past seven meetings and have lost only a Christmas Eve game in Green Bay over the past few years. The elements won’t be an issue here on a perfect day for football with light winds and 70-degree weather in the forecast. Dalvin Cook looks like he’s back to his old self and the offense is completely healthy, so we’ll get a look at just how improved the Packers defense truly is.
Chiefs (-7/53.5) at Raiders, 4:05 p.m. ET, CBS: The Chiefs will make their final scheduled trip to Oakland with the Raiders moving to Las Vegas next year, so this one promises to be spicy. Kansas City wasn’t slowed down by Jacksonville or by the loss of Tyreek Hill, who will miss at least a month with a shoulder injury. With Travis Kelce commanding all the attention in the middle of the field and Patrick Mahomes still able to get vertical through Sammy Watkins, Mecole Hardman and Demarcus Robinson, the Chiefs should continue to be the league’s most dangerous offensive team despite losing the fastest player on the roster. This should be a good test for that since the Raiders come in off a very nice defensive effort in beating the Broncos but lost hard-hitting rookie safety Johnathan Abram for the season due to a rotator cuff injury.
Kansas City really struggled against a rookie in Jacksonville’s Minshew, so it has something to prove against Derek Carr, who put the ball where it needed to be time after time in having his way with a Vic Fangio-led Broncos defense. If Darren Waller can continue to emerge as a top receiving target at tight end, we could get one last shootout at the Coliseum for old time’s sake if swirling winds aren’t a factor. Kansas City has won 10 of 12 in the series and three of four in Oakland following a 40-33 victory last season.
Saints at Rams (-2/52.5), 4:25 p.m. ET, FOX: New Orleans should get three free pass interference calls to help atone for getting robbed in the NFC Championship, but the good of this game coming so early in the season is that they get to bury it completely until at least January. The non-call haunted the Saints all offseason and even followed them into the opener with fans wearing stripes into the Superdome to get after the officials. The distraction wasn’t the reason they came so close to being upset by Houston but it certainly doesn’t help to live in the past. Getting out of that opener with a win and being able to turn the page by facing the Rams here should prove beneficial. It just remains to be seen how much the Saints have left after such a wild comeback win on a Monday night that left them facing the challenges of a short week and a trip to the west coast to help further throw off timing.
There’s also the possibility that they survived looking past the Texans and are going to tap into some well-deserved vengeance to hand the Rams a home loss at the Coliseum. Only DT Sheldon Rankins isn’t healthy enough to play, so they’ll at least be able to count on the bulk of the roster. Los Angeles won at Carolina last week but gave up a ton of yards and will be looking for improvement with safety Eric Weddle (concussion) and DT Michael Brockers (shoulder) set to play. Cooper Kupp, who tore his ACL in Week 10 and missed the postseason, looked sharp in his return last week and helps add a different dimension to the offense. Todd Gurley missed a practice this past week but seems to have his burst back too.
Bears (-2.5/40) at Broncos, 4:25 p.m. ET, FOX: Vic Fangio will have a good idea of what the Bears will be looking to accomplish on both side of the ball considering he ran the Khalil Mack-led defense against head coach Matt Nagy’s offense in practices all last season before making the jump to Denver this offseason. The Broncos lost his first game in Oakland and will look to capture the home opener for him against his former team. Inside linebacker Todd Davis is expected to return after missing all of training camp with a calf injury.
The Bears will be looking to get Mitchell Trubisky going and hope rookie David Montgomery can have as much success running the ball against the Broncos as Raiders’ first-year back Josh Jacobs did. Mack will look to keep Joe Flacco from getting comfortable and will look to extend Denver’s struggles as they’re on an 0-5 SU and ATS run. Chicago should see Eddie Goldman play through an oblique injury so the defense should come in intact. The Bears were 4-2 SU (3-3 ATS) as a road favorite.