2025 NFL Week 5 Betting Preview

By Jeff Stinger • September 30, 2025

A wild NFL Week 4 has led to an incredible NFL Week 5. The Rams and 49ers kick things off on Thursday. The Niners are desperate for a win while the Rams hope to put distance between themselves and their top rivals in the NFC West. On Sunday, Philadelphia brings an undefeated record into a home matchup against Denver, and the Commanders take on the Chargers in what’s already an important game for both teams. Check out NFL odds, analysis, and free picks for NFL Week 5.

Top 2025 NFL Week 5 Games to Bet On

The Eagles and Bills are getting comfortable at the top.

The Chargers and Ravens take tumbles.

It's Week 5 of the NFL power rankings. Here's where things stand. pic.twitter.com/7QFGbJKi75
— The Athletic (@TheAthletic) September 30, 2025

San Francisco 49ers vs. LA Rams

When: Thursday, October 2nd. 8:15 p.m. ET
NFL Week 5 Odds: 49ers +200 / Rams -250

The San Francisco 49ers are playing through injuries on both sides of the football. It’s the same old story: injuries have derailed the Niners’ last couple of seasons. Brock Purdy is back, but his offensive line will struggle against the Rams, who have one of the better pass rushes in the league.

Matthew Stafford to Puca Nacua is the top QB to WR connection in the league. Puca dominated the Colts in NFL Week 4. Rams cover.

2025 NFL 5 Pick: Rams

Minnesota Vikings vs. Cleveland Browns

When: Sunday, October 5th. 9:30 a.m. ET
NFL Week 5 Odds: Vikings -200 / Browns +160

Carson Wentz almost rallied the Minnesota Vikings against the Pittsburgh Steelers in Ireland on Sunday morning. He played well in the fourth quarter. But let’s be honest, Wentz put the Vikings in a hole by throwing a couple of picks. So we shouldn’t have too much faith in the former top draft pick.

Cleveland got smashed by the Lions in NFL Week 4. Detroit has one of the top offenses in the NFL, though. So Cleveland should bounce back. In their last two home games, the Browns upset the Green Bay Packers and lost to Joe Burrow and the Bengals by a point. Cleveland gets the nod.

2025 NFL 5 Pick: Browns

Las Vegas Raiders vs. Indianapolis Colts

When: Sunday, October 5th 28th. 1:00 p.m. ET
NFL Week 5 Odds: Raiders +240 / Colts -303/

Although Staff and Puca went nuts, the truth about Indy’s loss against the Rams in NFL Week 4 is that the Colts shot themselves in the foot. Daniel Jones came back to earth by throwing two picks.

Indianapolis should find the going much easier versus the Raiders. Still, 6.5 points feels like a lot considering that Ashton Jeanty went off with a pair of touchdown catches and a rushing TD. Jeanty can keep it going versus a Colts D that is good but doesn’t shut down teams. Also, Geno Smith is playing well. Brock Bowers could have a massive game in this if you’re playing fantasy. Take the points if you’re betting the game.

2025 NFL 5 Pick: Raiders

Denver Broncos vs. Philadelphia Eagles

When: Sunday, October 5th. 1:00 p.m. ET

NFL Week 5 Odds: Eagles +4.5 / Buccaneers -4.5

The 4-0 Eagles could be set up for a straight-up loss. First, the betting line is only at -4.5, despite the Broncos playing the Bengals on Monday night and facing the Eagles after a short week.

Second, Denver’s Bo Nix has begun to pick it up, throwing 4 TDs to a single pick in weeks 2 and 3. Finally, the Eagles’ defense gave up 26 points to the Rams in a miracle finish, where they returned a blocked field goal to push their total to 33 on the game’s final play, and 25 to the Bucs in NFL Week 4. The Broncos cover regardless of the spread and have a real shot of taking the moneyline.

2025 NFL 5 Pick: Broncos

Washington Commanders vs. LA Chargers

When: Sunday, October 5th. 4:25 p.m. ET
NFL Week 5 Odds: Commanders +125 / Chargers -149

The Chargers were flat versus the New York Giants in NFL Week 4. LAC showed up with no fire. They had no energy, and it cost them a game they were supposed to win easily.

John Harbaugh isn’t going to let his squad show up flat in this. The Commanders aren’t good enough to beat the Bolts on the road. Washington is solid, yes, but even if Jayden Daniels plays, he’ll be rusty, and Justin Herbert should bounce back after his poor performance against NYG.

2025 NFL 5 Pick: Chargers

Kansas City Chiefs vs. Jacksonville Jaguars

When: Monday, October 6th. 8:15 p.m. ET
NFL Week 5 Odds: Chiefs -175 / Jaguars +145

The Chiefs got back to .500 after a stunning 37-20 win over the Ravens. Ah, but how lovely was it, really? Sure, Patrick Mahomes lit up the Ravens’ D. But who hasn’t?

Baltimore allows 33.3 points per game. The Jags’ defense is the best in the NFL in turnover margin. That makes the Jaguars a massive overlay at +3. Jacksonville is 3-1 this season and hosts KC a week and a day after beating San Francisco 26-1 at Levi’s Stadium. The Jags are worth a look on the ML and should cover.

2025 NFL 5 Pick: Jaguars

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*All stated odds are subject to change without prior notice.

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