The first four weeks of the 2025 season are really a feeling-out period to figure out the true identities of all 32 teams. Some teams are easier to read than others and what types of performances to expect from week to week, depending on location, talent and quality of opponent. Others remain inconsistent enigmas.
Trends can become a bigger factor in the picks and predictions against the spread. Week 5 brings a little break with four teams on bye and two fewer games than a full slate. That makes less that can go wrong, but also two fewer chances to be right.
Here's diving into the latest fearless forecast of professional pigskin prognostications from Thursday to next Monday:
(Odds courtesy of Caesars Sportsbook)
POWER RANKINGS: Rams, Steelers and Chiefs bump up; Ravens, 49ers fade for Week 5
NFL picks against the spread for Week 5
Game of Midweek: Rams (-3.5, 47 o/u) at 49ers
Thursday 8:15 p.m. ET, Amazon Prime Video
The 49ers used to dominate Sean McVay's Rams with Kyle Shanahan, but that record is down to 10-7, including playoffs. The Rams are the healthier and better all-around team to trust, the second-best in the NFC. But San Francisco will be game for its rivals on a short week with Brock Purdy and the offense playing better. It just won't be enough vs. red-hot Matthew Stafford and his elite veteran wide receivers.
Pick: Rams win 27-24 but fail to cover the spread.
Game of the Week: Chiefs (-3, 45.5 o/u) at Jaguars
Monday 8:15 p.m. ET, ESPN/ABC
The Chiefs' offense has unlocked plenty for Patrick Mahomes with the return of Xavier Worthy as the passing game looks fully loaded again. The Jaguars' defense has been playing well, active in forcing takeaways. But the Chiefs' defense also remains all-around solid and can cause some coverage problems for Trevor Lawrence after containing Travis Etienne's big running.
Pick: Chiefs win 24-20 and cover the spread.
Lock of the Week: Eagles (-4.5, 43.5 o/u) over Broncos
Sunday 1 p.m. ET, CBS
The Eagles are in a total groove in reading the opponent on how much to be aggressive or conservative, run or pass. Jalen Hurts makes everything possible with the pivot because he is a comfortable toggling dual threat, no matter what receivers might be carping. Philadelphia might have some issues throwing downfield against Denver's defense, but this feels like another game in which Saquon Barkley carries things.
Pick: Eagles win 34-20 and cover the spread.
Upset of the Week: Buccaneers (+3, 44.5 o/u) at Seahawks
Sunday 4:05 p.m. ET, CBS
The Buccaneers saw their first failed valiant comeback of the season with Baker Mayfield against those Eagles. He will be ready to outduel fellow former Panthers castoff QB Sam Darnold in Seattle. Tampa Bay can cause issues by taking away the run, which is critical to Darnold's downfield passing. The Seahawks' defense will have more problems with the Bucs' balance and explosiveness.
Pick: Buccaneers win 24-20.
Vikings (-3.5, 37 o/u) at Browns
Sunday 9:30 a.m. ET, NFL Network (in London, England)
The Vikings stay across the pond with a skip over from Dublin after a rough offensive time against the Steelers. The Browns' defense isn't a fun follow-up with Myles Garrett after Pittsburgh's pass rush demolished Carson Wentz. But at least the Vikings' defense will get breaks from big plays and can force Joe Flacco into more key turnovers and maybe this time, the bench.
Pick: Vikings win 23-14 and cover the spread.
Raiders at Colts (-6.5, 48.5 o/u)
Sunday 1 p.m. ET, Fox
The Raiders are melting down in the passing game with Ashton Jeanty becoming the total centerpiece of the offense. The Colts can counter well with red-hot Jonathan Taylor and also shred the Raiders' coverage on intermediate routes with Daniel Jones throwing to Michael Pittman Jr. and Tyler Warren.
Pick: Colts win 31-20 and cover the spread.
Giants (-1.5, 41.5 o/u) at Saints
Sunday 1 p.m. ET, CBS
The Giants will feel it more on the road with Jaxson Dart as no Malik Nabers won't hurt much here on the road as he and fellow rookie Cam Skattebo spark a strong complementary performance to keep the defense hot on the road vs. Spencer Rattler.
Pick: Giants win 23-20 and cover the spread.
Cowboys (-2.5, 46.5 o/u) at Jets
Sunday 1 p.m. ET, Fox
Dak Prescott is rolling in Brian Schottenheimer's sizzling system and the Jets' defense is even more dysfunctional than Dallas'. The Jets have the weapons around Justin Fields to keep it interesting for a while, until too many big plays are yielded to Prescott.
Pick: Cowboys win 27-20 and cover the spread.
Imagn
Dolphins (-1.5, 45 o/u) at Panthers
Sunday 1 p.m. ET, Fox
The Panthers are much better offensively at home with Bryce Young and Chuba Hubbard and also play more inspired defense in Charlotte. That will be the case again as they get after Tua Tagovailoa inside and outside while Young regains his confidence with a big passing day to outduel fellow Alabama product Tua.
Pick: Panthers win 24-21.
Texans at Ravens (-3.5, 46 o/u)
Sunday 1 p.m. ET, CBS
Houston found more of its running game in Week 5 and they also have a big-play, go-to wide receiver in Nico Collins. That will allow C.J. Stroud to produce well to keep up with a hamstring-hampered Lamar Jackson. But Baltimore has a little extra juice to save its fading 1-3 season than the visitors.
Pick: Ravens win 24-21 but fail to cover the spread.
Titans at Cardinals (-9.5, 40.5 o/u)
Sunday 4:05 p.m. ET, CBS
Cam Ward is looking for his first win as a 2025 No. 1 overall pick. Kyler Murray hasn't played that well as the 2019 edition of that QB. This screams ugly defensive fest with the desert as a backup drop for Arizona to run Tennessee dry.
Pick: Cardinals win 24-14 and cover the spread.
Lions (-8.5, 49 o/u) at Bengals
Sunday 4:25 p.m. ET, Fox
The Lions will be ready to tame the other cats with more help on defense and also outscore them with Jared Goff using mismatches for Amon-Ra St. Brown, Jameson Williams, and Jahmyr Gibbs. This type of fun shootout is where Cincinnati will miss Joe Burrow most.
Pick: Lions win 27-20 but fail to cover the spread.
Commanders at Chargers (-2.5, 47.5 o/u)
Sunday 4:25 p.m. ET, Fox
The Commanders are hoping Jayden Daniels can return for Marcus Mariota at QB but the offense is faring OK with Kliff Kingsbury's system well in place, spreading the ball around. The defense is becoming a bigger issue, giving up chunks vs. the run and other big plays. That won't change vs. Justin Herbert and Omarion Hampton on the road.
Pick: Chargers win 24-20 and cover the spread.
Patriots at Bills (-8.5, 50 o/u)
Sunday 8:20 p.m. ET, NBC and Peacock
The Patriots' offense is hitting its expected stride with Josh McDaniels revving up Drake Maye and weapons who are suddenly looking better overall. They'll be ready to play tough for Mike Vrabel in this tough division test, but in the end, Josh Allen and James Cook will be too much for a defense that isn't as good on the road.
Pick: Bills win 34-27 but fail to cover the spread.
Stats of the Week
- Week 4 record straight up: 10-3
- Week 4 record against the spread: 6-8
- 2025 season record straight up: 45-16
- 2025 season record against the spread: 29-32