Best NFL Week 4 Picks Against the Spread for Jags-Bengals, Rams-Eagles, 49ers

NFL Week 4 got underway on Thursday Night in a Browns win vs. the division rival Steelers, and continues on Sunday morning across the pond, with Commanders-Colts at 9:30 a.m. ET. To follow that up, there are 13 mrre games taking place before Sunday Night Football, beginning at 9:30 a.m. ET, with a London clash that features the Indianapolis Colts and Washington Commanders.

Ahead of Sunday's NFL Week 4 games on Sunday, October 4, which teams are the right NFL picks to cover the spread?

Below, we’ll discuss our favorite NFL Week 4 picks against the spread, featuring the live spread, winner, and over/under payouts from PrizePicks — available nationwide!

Make NFL Week 4 picks on spreads, totals, and winners on PrizePicks!

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Best NFL Week 4 Picks Against the Spread, Game Predictions

Here are our best NFL Week 4 picks against the spread, including each game’s payouts on PrizePicks. NFL Week 4’s predictions include the Rams, Jaguars, and 49ers.

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

Rams vs. Eagles Prediction on Spread – Sunday, October 4

Time: 1 p.m. ET

A second-half collapse against the Denver Broncos to fall to 1-2 on the season was less than ideal for the Los Angeles Rams in Week 3, but they’re expected to get WR Puka Nacua back in some capacity in Week 4 against the Philadelphia Eagles. Nacua has been inactive since Week 2 with a hip/groin injury, though he’s been a full participant in practice leading up to Sunday’s game.

Even with Nacua sidelined early in the year, the Rams are one of five teams ranked 13th or better in offensive (45.0%) and defensive success rate (42.0%), per rbsdm. Since QB Matthew Stafford and head coach Sean McVay became a pair in 2021, Los Angeles has the eighth-best cover rate against the spread (ATS) as road favorites (58.3%) with a 14-10 record in those scenarios. 

On the other hand, the Eagles looked lifeless on the road against the QB Case Keenum-led Chicago Bears in Week 3, losing 27-7. Despite Philly returning home in Week 4, matters could get even worse for an Eagles’ offense that is already 28th in success rate (38.0%), with WR DeVonta Smith dealing with a hamstring injury.

Since the start of last season, the Eagles have gone 4-6 ATS when playing at Lincoln Financial Field. On top of that, Philadelphia has failed to cover the spread in their first three games in 2026, and Los Angeles has been the better overall team so far, despite the losing record.

Make your Rams vs. Eagles prediction and pick against the spread on PrizePicks!

Jaguars vs. Bengals Prediction on Spread – Sunday, October 4

Time: 1 p.m. ET

One of the most anticipated matchups in Week 4 pits the Jacksonville Jaguars against the Cincinnati Bengals. Both teams are 2-1 through the first three weeks, but the Jaguars are the best overall team the Bengals have faced by a wide margin.

QB Trevor Lawrence has Jacksonville’s offense firing on all cylinders, logging the ninth-most adjusted EPA/play (0.25), fifth-highest success rate (53.1%), and second-highest completion percentage over expected (CPOE; +8.6%) among 33 QBs with 50-plus plays. Meanwhile, the Jaguars’ defense has allowed the 4th-fewest EPA/play (-0.11) and the 13th-lowest success rate (42.2%).

After dismantling the reigning AFC champions (New England Patriots) 35-6 in Week 3, the Bengals’ defense took a major step back against QB Aaron Rodgers and the Pittsburgh Steelers. Rodgers carved up Cincy for 290 yards and 3 TDs in Week 3, and RB Jaylen Warren totaled 176 scrimmage yards out of the backfield.

Although QB Joe Burrow can catch fire at any moment, he’s just 15th in adjusted EPA/play (0.15) and 17th in success rate (47.5%) among 33 QBs with 50-plus plays across the first three weeks. Burrow has missed time since the start of last season, but it’s still worth noting that Cincinnati is just 5-5 ATS at home and 4-4 ATS as favorites during that span.

Make your Jaguars vs. Bengals prediction and pick against the spread on PrizePicks!

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Broncos vs. 49ers Prediction on Spread – Sunday, October 4

Time: 4:25 p.m. ET

Emotions are running high in Denver after the Broncos mounted a Week 3 comeback against the Rams, coming back from 16-0 at halftime. The Broncos’ reward for that effort is a trip to face the San Francisco 49ers at Levi Stadium on Sunday.

San Francisco’s QB Brock Purdy-led offense leads the league in both EPA/play (0.33) and success rate (56.0%) entering Week 4. The 49ers’ defense appears to be a run-funnel unit (9th in dropback success rate, 32nd in rush success rate allowed), which isn't ideal for a Broncos team that ranks 22nd in offensive rushing success rate (35.8%).

When comparing metrics between Purdy and QB Bo Nix, San Francisco has a major edge under center. Of the 33 QBs with 50-plus plays this year, Purdy is first in adjusted EPA/play (0.63) and success rate (64.9%) — he's had an incredible start to his season.

As for Nix, he ranks 26th in adjusted EPA/play (-0.02) and 24th in success rate (44.7%) in his first three games back from an ankle injury he suffered in last year’s playoff run for the Broncos. Denver has been outscored 40-10 in the first half of their games this season, and another slow start won’t fly against an efficient San Fran squad.

Make your Broncos vs. 49ers prediction and pick against the spread on PrizePicks!

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Make NFL Week 4 Predictions on PrizePicks

Desperation can generate special performances from talented teams, and the Rams need one to avoid a 1-3 start to the season against the Eagles in Week 4. Besides the Rams, the Jaguars and 49ers are teams that could potentially be poised for success on Sunday.

Don’t wait until kickoff to lock in your action in Week 4 — make your 2026 NFL picks on PrizePicks now and earn real money if you’re right.

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