Best NFL Week 5 Picks Against the Spread: Back the Jaguars, Vikings?

Following a Thursday Night Football matchup between the Tampa Bay Buccaneers and Dallas Cowboys, there are 11 NFL games taking place on Sunday, October 11, before Sunday Night Football. That 11-game slate will begin with the Philadelphia Eagles squaring off against the Jacksonville Jaguars in London on Sunday morning.

Before Week 5 NFL games kick off on October 11, which teams are ideal picks to cover the spread?

Below, we’ll discuss our favorite NFL Week 5 picks against the spread, featuring winner, spread, and over/under payouts on PrizePicks.

Make NFL Week 5 picks on spreads on PrizePicks!

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Best NFL Week 5 Picks Against the Spread, Game Predictions

Here are our best NFL Week 5 picks against the spread, including each game’s payouts on PrizePicks. NFL Week 5’s predictions include the Jaguars, Vikings, and Broncos.

PrizePicks payouts are live as of this writing and subject to change.

Eagles vs. Jaguars Prediction on Spread – Sunday, October 11

Time, How to Watch: 9:30 a.m. ET on NFL Network

Ahead of Sunday’s London game between the Eagles and Jaguars, vibes are trending in different directions for these teams. In addition to injuries to WR DeVonta Smith, RB Saquon Barkley, and RB Tank Bigsby, All-Pro RT Lane Johnson announced his retirement earlier this week.

Even with Philly hiring Sean Mannion as the team’s offensive coordinator in hopes of improving from last season’s woeful play, the Eagles are 30th in dropback success rate (38.2%) and 25th in rushing success rate (34.4%), per RBSDM.

Philadelphia’s defense is also 23rd in dropback success rate (48.4%) and 28th in rushing success rate (44.7%) allowed, which is not ideal against an ultra-efficient Jacksonville offense.

On top of QB Trevor Lawrence leading the Jaguars’ offense to the eighth-highest dropback success rate (50.4%) and fifth-highest rushing success rate (46.3%), their defense is sixth in dropback EPA (-0.02) and seventh in rushing EPA (-0.15) allowed this season. E

Entering Week 5, Lawrence has the fourth-lowest payout to win NFL MVP (8.33x) on PrizePicks.

Since the start of last season, the Jaguars carry a league-best 9-2 record against the spread (ATS) when playing as a favorite, per Team Rankings. Meanwhile, the Eagles are 0-4 ATS to begin the 2026 campaign.

Make your Eagles vs. Jaguars prediction on PrizePicks!

Vikings vs. Saints Prediction on Spread – Sunday, October 11

Time, How to Watch: 1:00 p.m. ET on FOX

The Minnesota Vikings are undefeated across the first four weeks despite the team’s offense lacking consistency. However, QB Kyler Murray and Minnesota’s offense are in a perfect get-right spot on the road against the New Orleans Saints in Week 5.

Murray could finally play his first full game with WR Justin Jefferson on Sunday, with Jettas officially questionable due to an ankle injury. The Vikings' QB will face a Saints defense that is 30th in dropback success rate (52.4%) and 32nd in rushing success rate (52.7%) allowed.

Meanwhile, the Vikings’ blitz-heavy defense under defensive coordinator Brian Flores is first in dropback success rate (33.8%) and rushing success rate (28.1%) allowed.

Not only are the Saints coming off a disappointing Week 4 loss to the Atlanta Falcons at home, but QB Tyler Shough has been plagued by slow starts this season. Of the 27 QBs with 50 or more first-half plays, Shough is 21st in adjusted EPA/play (-0.03) and 23rd in success rate (40.0%).

In comparison, Shough has the 10th-best adjusted EPA/play and sixth-best success rate (53.4%) among 25 QBs with 50 or more second-half plays.

Besides the Vikings being 3-1 ATS to begin 2026, they are 6-3 ATS as the visiting team since the beginning of 2025. As for the Saints, they’ve failed to cover the spread in back-to-back games, and they are 1-4 ATS as a home underdog since the start of last season.

Make your Vikings vs. Saints prediction on PrizePicks!

Broncos vs. Chargers Prediction on Spread – Sunday, October 11

Time, How to Watch: 4:05 p.m. ET on CBS

The Denver Broncos have been far from steady early in the season, but they’ve had to face the Chiefs, 49ers, Rams, and Jaguars through the first four weeks. Next up for the Broncos is a Los Angeles Chargers squad that is winless and 0-7 ATS in their last seven games.

Even though Denver could be sans CB Pat Surtain II and CB Riley Moss in Week 5, Los Angeles could be without WR Ladd McConkey, WR Quentin Johnston, and RT Joe Alt on Sunday.

Aside from the Broncos logging the fourth-highest blitz rate (40.4%), QB Justin Herbert has the sixth-highest turnover-worthy play rate (8.3%) and seventh-highest pressure-to-sack rate (17.9%) among 19 QBs with at least 25 dropbacks under pressure in 2026, per PFF.

The Chargers’ offense has been a mess despite the addition of offensive coordinator Mike McDaniel, ranking 29th in dropback EPA (-0.12) and 25th in rushing EPA (-0.19).

Since Sean Payton became the head coach of the Broncos in 2023, the team has the 12th-best record ATS (17-14-1) as a favorite during that span. On the flip side, the Chargers have the 10th-worst record ATS (3-3-1) as an underdog since the start of last season.

Make your Broncos vs. Chargers prediction on PrizePicks!

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Make NFL Week 5 Predictions on PrizePicks

The first month of the 2026 NFL season is complete, and we’re getting a better idea of which teams are legitimate contenders. With an assortment of solid matchups in Week 5, the Jaguars, Vikings, and Broncos are in prime spots to defeat their opponents on Sunday.

Don’t wait until kickoff for this week of NFL action — make your NFL Week 5 picks on PrizePicks now and earn real money if you’re right.

With the season underway, just pick NFL players, predict More or Less on their stats, and cash in if you’re right. With Team Picks, you can make predictions on NFL game winners, spreads, over/unders, and award futures, now available in 36 states.

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