Week 2 of NFL action was a wild one and should have a huge long-term effect on the league given the number of key injuries from coast-to-coast. Those fresh faces at quarterback have resulted in a big unknown in terms of a few lines going into a critical weekend of action featuring a number of juicy matchups while a handful of teams are battling for what feels like their season's fate already going into game No. 3.
Note: All times are ET and all games are on Sunday, Sept. 22
Here are this week's best NFL picks against the spread:
Detroit (1-0-1) at Philadelphia (1-1), 1 p.m. ET
The injury report for the Eagles is lengthy and impactful following that close loss on the road to Atlanta last week but the Eagles return home to the Linc for a key matchup against a Lions side that is kicking themselves for not sitting at 2-0 on the season. Matt Patricia's squad did well against the Chargers in the red zone at home but taking that kind of performance out of Ford Field will be a challenge. Also keep in mind that the home team is a second-half squad, which is exactly when Detroit seems to take the foot off the pedal a bit. Don't be surprised if Philly takes care of business in this one. The Pick: Eagles -6.5
Oakland (1-1) at Minnesota (1-1), 1 p.m. ET
It only took a week for Jon Gruden to go from feeling okay about his revamped defense to wondering what else will go right on that side of the ball after the Chiefs tossed the ball all around the infield dirt at the Coliseum in a disappointing loss. Defending MVP Patrick Mahomes will do that to just about everybody however and rising up to that level isn't quite what their next opponent does with regularity in Kirk Cousins. The Raiders have the offensive line to protect Derek Carr enough against that Vikings front seven to keep this one a lot closer than the experts think in the end. The Pick: Raiders +9
Miami (0-2) at Dallas (2-0), 1 p.m. ET
How 'bout them Cowboys? Jerry Jones' squad is living up to the preseason billing and look like a Super Bowl contender so far on both sides of the ball. Dak Prescott clearly looks like he's playing for that mega contract extension and has been terrific off play-action passes in Kellen Moore's new offense. Miami, meanwhile, just traded away one of their best young defenders and have been hearing all week about going 0-16 whenever they turn on a TV — quite a demoralizing tone after getting blasted by the Patriots. Big D rolls again while trying to make a statement at home. The Pick: Cowboys -21.5 and Under 47.5
Pittsburgh (0-2) at San Francisco (2-0), 4:25 p.m. ET
These two teams are headed in opposite directions and you can look no further than the quarterback position as to why. Naturally, Ben Roethlisberger's season-ending injury is the talk of the Steel City and while the franchise has a lot of faith in new starter Mason Rudolph, making his first start on the road is a tough ask of anybody. Meanwhile, Jimmy Garoppolo and company seemed to hit their stride against Cincinnati and finally look like the kind of team we all envisioned Kyle Shanahan having. Injuries are obviously pressing for both teams but given Pittsburgh's atrocious record on the West Coast combined with everything swirling around the team, the home side is the easy lean here. The Pick: 49ers -6.5
Last Week: 3-1
— Written by Bryan Fischer, an award-winning college football columnist and member of the Athlon Contributor Network. You can follow him from coast-to-coast on Twitter, Instagram and Snapchat at @BryanDFischer.