The first month of the 2025 NFL schedule is in the books, with all 32 teams playing four games apiece. October brings the arrival of bye weeks, with four teams (Atlanta Falcons, Chicago Bears, Pittsburgh Steelers, and Green Bay Packers) not taking part in the NFL schedule this week.
Ahead of a slate of action with plenty of intriguing matchups, let’s dive into our NFL Week 5 predictions for every game this week.
Los Angeles Rams 24, San Francisco 49ers 17
Injuries have once again taken a toll on the San Francisco 49ers. In their first game without Nick Bosa, San Francisco allowed 6.5 yards per carry and 124 rushing yards to Travis Etienne while failing to record even a single quarterback hit or sack. On top of that, the 49ers’ offensive line struggled to protect Brock Purdy. Now, the 49ers face a Los Angeles Rams team that just recorded a 48.6 percent pressure rate against the Colts’ offensive line, and this Rams’ offense is averaging 4.5 yards per carry this season. Thursday Night Football games tend to be fairly close, but Los Angeles has the big advantages that should result in a win.
Minnesota Vikings 17, Cleveland Browns 13
Football fans in London will get to witness two quarterbacks with awful decision-making when pressured taking on two of the best pass rushes in the NFL. The Cleveland Browns defense allows the lowest yards-per-play average (4.1) in the NFL, while the Vikings rank top six in sack rate, third-down defense, and yards per drive (22.6). Sam Darnold and Carson Wentz will likely both throw an interception in this game, so whichever defense generates the most takeaways might be the deciding factor. In a tight game, the offense with Justin Jefferson, Jordan Addison, and T.J. Hockenson should make enough plays to pull out the victory.
Indianapolis Colts 27, Las Vegas Raiders 21
The Indianapolis Colts and Las Vegas Raiders are both coming off losses in which their quarterbacks were picked off multiple times. Looking ahead to this matchup, the key will be which team can run the football more effectively. Indianapolis has a bottom-10 run defense in yards per carry (4.5) this season, but the Raiders’ run game has been wildly ineffective (3.1 yards per carry) until last week versus Chicago. As for Las Vegas’ ability to defend the run, it allowed 201 yards to the Commanders but held its three other opponents under 100 total rushing yards. The pick here comes down to the team with the better offensive line and the consistently more effective ground game, but the Raiders can pull off the road win if Geno Smith avoids turnovers.
New York Giants 20, New Orleans Saints 17
The New York Giants offense without Malik Nabers will be almost close to unwatchable. Fortunately for New York, its defensive line is coming off a season-best performance and now gets to take on a young quarterback (Spencer Rattler) who has really struggled with pressure this season. Neither quarterback will play particularly well in this game, but the Giants have the defensive advantage and Dart should make enough plays with his arm to pull out his second career win.
Philadelphia Eagles 17, Denver Broncos 13
It’s a matchup in NFL Week 5 between two of the least effective passing offenses in the league. At least the Denver Broncos have a bit of an excuse, with quarterback Bo Nix playing poorly despite having a good offensive line protecting him. For Philadelphia, coming in averaging just 138 pass yards per game (31st in the NFL), there’s less of an excuse. Denver’s exceptional defense does provide it with a chance to pull off the surprise win at Lincoln Financial Field, especially since Sean Payton will exploit the vulnerabilities this Eagles defense has against the run and at the No. 2 corner spot. However, you can run the football on Denver. Saquon Barkley and Jalen Hurts will do just enough for Philadelphia to escape with a 5-0 record.
Carolina Panthers 28, Miami Dolphins 27
There should be no shortage of points in this Week 5 afternoon draw between the Miami Dolphins and Carolina Panthers. While this Panthers offense hasn’t exactly been good through four games, it still has the talent and scheme to take advantage of a Dolphins defense that can be exploited on the ground (145 rush yards per game) and through the air (128.9 QB rating allowed). Likewise, Carolina doesn’t have the pass rush to make Tua Tagovailoa uncomfortable. It will come down to who can score late in the fourth quarter, with Bryce Young leading the go-ahead drive that delivers the Panthers their second win of the year.
Houston Texans 23, Baltimore Ravens 13
The fact that we only have C.J. Stroud and Co. putting up 23 points against this Baltimore Ravens defense should tell you everything about the Houston Texans’ offensive line. Even an injury-decimated Ravens defense will be able to generate pressure on Stroud. However, the Lamar Jackson injury (hamstring) is a death blow for this Ravens offense. Houston will be able to run the football on Baltimore, and just a few clean pockets will allow Stroud to hit Nico Collins deep. The best performance, though, will come from this Texans defense suffocating the life out of a Baltimore offense led by Cooper Rush.
Arizona Cardinals 27, Tennessee Titans 16
Coming off a pair of tough losses versus intradivision opponents, this should be a get-right game for the Arizona Cardinals. Unfortunately for Cam Ward, the Tennessee Titans can’t protect the rookie quarterback, and the play-calling is just as bad as the offensive line. It’s an appetizing matchup for a Cardinals defense that ranks fifth in scoring defense (18.5 points per game allowed) and has the ninth-highest sack rate in the NFL. Arizona should win this one comfortably.
Tampa Bay Buccaneers 20, Seatlte Seahawks 17
It’s a matchup between two of the league’s best defenses and dark horse contenders in the NFC. The Tampa Bay Buccaneers came up short in their efforts to take down Philadelphia, but self-inflicted wounds played a part in that. Meanwhile, the Seattle Seahawks are riding high on a three-game win streak, thanks in large part to Mike Macdonald’s defense. Both defenses won’t give up big plays and should do an effective job neutralizing the run game. The deciding factor is which quarterback fares better versus pressure and is more reliable in critical situations, which is Baker Mayfield.
Related: NFL Defense Rankings 2025
Detroit Lions 34, Cincinnati Bengals 21
The Detroit Lions should have no trouble dispatching the Jake Browning-led Cincinnati Bengals. It’s a one-sided matchup that should start with the Lions defense feasting on a bottom-10 offensive line, forcing Browning into multiple interceptions. With great field position, Detroit keeps Jared Goff’s jersey clean, and this Lions offense finishes the day with another 30-burger.
Washington Commanders, 23, Los Angeles Chargers 20
The expectation here is that Jayden Daniels returns in Week 5, flipping this matchup in the Washington Commanders’ favor. That has a lot to do with the fact that, without its two offensive tackles, the Los Angeles Chargers are allowing Justin Herbert to be pressured on more than 50 percent of his dropbacks. Washington (3.6 yards per carry allowed) can bottle up Omarion Hampton, and with Dan Quinn able to generate pressure without blitzing because of the Chargers’ tackle situation, the Commanders will return home from Los Angeles with a 3-2 record.
Buffalo Bills 27, New England Patriots 20
The good news for the New England Patriots heading into this Sunday Night Football matchup is that their pass defense looks a lot better with Christian Gonzalez back on the field. Josh McDaniels also might have a fair amount of success feeding the football to TreVeyon Henderson and Rhamondre Stevenson against a Buffalo Bills defense that allows 164 rush ypg and over 6 yards per carry. That at least creates an opportunity for an upset on primetime, but it would be foolish to pick against Josh Allen evading the Patriots’ pass rush and exploiting the other issues in New England’s secondary.
Jacksonville Jaguars 24, Kansas City Chiefs 21
The 2025 NFL season has already delivered quite a few surprises, and we believe another one is coming in Week 5 on Monday Night Football. Liam Coen’s Jacksonville Jaguars have the second-best rushing offense in the NFL, averaging 144 yards per game and 5 yards per carry. Opponents have had success running on this Kansas City Chiefs defense, which allows 127 rushing yards per game and a 4.9 yards per carry average. While Patrick Mahomes won’t gift this Jaguars defense as many interceptions as other teams have (nine), sacks and forced incompletions are something Jacksonville’s pass rush can create versus this Chiefs offensive line.
