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NFL Week 5 Picks Against the Spread

NFL Week 5 Picks Against the Spread

Publish Date: September 30, 2025

The NFL season is here. Picking NFL games straight up is hard enough, but picking against the spread is even tougher. Here are NFL week 5 picks against the spread. (Spreads are from Tallysight as of Tuesday morning)

Last Week: 8-8

Season: 32-32

Thursday Night Football

San Francisco 49ers at Los Angeles Rams (-5.5)

The 49ers are coming off a loss to the Jaguars this week. Offensively, there is still a lot to be desired. The Rams have the offense rolling, scoring 28.7 points per game over their last three. They should be able to win and cover.

Pick: Rams

Sunday Morning

Minnesota Vikings (-3.5) at Cleveland Browns (Game in London)

Minnesota stayed overseas after their loss to the Steelers. The extra time can benefit them, but also their defense can really limit what the Browns can do.

Pick: Vikings

Sunday Afternoon

Dallas Cowboys (-2.5) at New York Jets

The Cowboys’ offense is great and the defense is not. While the Jets have a better defense, it is hard to see them keeping up with the Cowboys’ high-powered offense on a short week.

Pick: Cowboys

Las Vegas Raiders at Indianapolis Colts (-7)

The Colts suffered their first loss of the season to the Rams. Their defense faltered and they made too many mistakes. Las Vegas saw more production out of the running game and if Geno Smith can limit the turnovers, the Raiders can keep it close, even in a loss.

Pick: Raiders

New York Giants at New Orleans Saints (-1.5)

Jaxson Dart seemed to bring life to the Giants. They can go on the road and defeat the winless Saints in large part due to their pass rush being able to get pressure on the quarterback.

Pick: Giants

Denver Broncos at Philadelphia Eagles (-3.5)

Philadelphia is getting their offense going over the last two weeks. The Broncos have a quality defense, but are on a short week and still have some issues offensively. The Eagles can win and cover at home.

Pick: Eagles

Miami Dolphins at Carolina Panthers (-1.5)

Carolina came back down to earth after destroying the Falcons by getting out by the Patriots. Miami lost Tyreek Hill to injury on Monday Night Football, but their offense got back to playing good football. They can pull off the win on the road.

Pick: Dolphins

Houston Texans at Baltimore Ravens (-3)

Lamar Jackson left the game against the Chiefs and is questionable. The Ravens desperately need a win, so he may suit up if he is able. Houston’s offensive line has major issues that the Ravens can exploit to help them get the win.

Pick: Ravens

Sunday Evening

Tennessee Titans at Arizona Cardinals (-9.5)

Tennessee isn’t playing well this season, but this is a large spread for the Cardinals to cover. Arizona has lost their last two games and have not won a game by more than seven points this season. Tennessee will likely lose, but can keep it close.

Pick: Titans

Tampa Bay Buccaneers at Seattle Seahawks (-3.5)

Seattle’s defense and Tampa Bay’s offensive line could give the Seahawks the early edge. The Buccaneers are playing really well despite the line issues and Baker Mayfield can keep this close, if not win this outright. If the Bucs get up early, the Seahawks could struggle to play catch up.

Pick: Buccaneers

Detroit Lions (-9.5) at Cincinnati Bengals

The Bengals are a mess and are on a short week. Detroit should be able to score at will on the road to cover this large spread.

Pick: Lions

Washington Commanders at Los Angeles Chargers (-2.5)

The Commanders could still be without Jayden Daniels, which will make things tough on the road. Los Angeles lost a tough one on the road to the Giants, but the Commanders don’t pose the same defensive issues. They should win and cover at home.

Pick: Chargers

Sunday Night Football

New England Patriots at Buffalo Bills (-7.5)

Buffalo is on a tear right now. After their big comeback win against the Ravens in week 1, they have won every game by two scores. New England is too inconsistent to keep up.

Pick: Bills

Monday Night Football

Kansas City Chiefs (-3) at Jacksonville Jaguars

The Chiefs have put things back on the right track by winning their last two games and they’ve looked good. Jacksonville just won on the road against the 49ers and are 3-1, but beating the Chiefs, even at home, is a different challenge.

Pick: Chiefs

 

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