The San Francisco 49ers’ 2025 season is like buying a new car.
It has all the bells and whistles, and the specs and reviews are impressive. But the second you drive it off the lot, it immediately loses value.
The Niners enter this year with plenty of standouts on both sides of the ball and the weakest schedule in the league. The NFL odds are giving San Francisco a glowing projection, setting the 49ers as favorites in 15 games — second most in the NFC.
But once Week 1 hits...
Many of San Francisco’s key players — the ones that stuck around - are aging, and a lot of those stars are coming off injuries, putting their durability in question. Behind those stalwarts is a depth chart of unproven talents and ho-hum veterans.
Do the Niners have that “new car” smell, or are football bettors looking at a lemon that went 5-12 ATS in 2024?
I kick the tires on the San Francisco 49ers with my 2025 NFL betting preview.
San Francisco 49ers best bets
Read on for Jason's full analysis and San Francisco 49ers breakdown!
San Francisco 49ers odds for 2025
| Market |  |
|---|---|
| Win Super Bowl | +2000 |
| Win conference | +750 |
| Win division | +160 |
| Make playoffs | -200 |
| Over 10.5 wins | -110 |
| Under 10.5 wins | -110 |
Best futures bet: Win NFC West (+160)
You can’t handicap for injuries that haven’t happened yet, but considering the medical history of the 49ers, you have to expect some standouts to miss time.
Still, this +160 return is a deal considering San Francisco was -195 in this same market last year and is a look-ahead favorite in 15 of 17 games this season.
Ten of those look-ahead spreads have the Niners laying more than a field goal. Favorites of -3.5 or higher win at a 73% clip the past four seasons.
If San Francisco somehow avoids the injury bug, it can cruise to 11 wins. But even if it does lose some games to injuries, it might not need 11 victories to take the NFC West.
The Niners get a big boost in the home stretch of the schedule (more on that below), which is more than Arizona and L.A. can say. There could be five or six wins waiting in the final two months, pushing the 49ers back to the top of the NFC West.
San Francisco 49ers at a glance: Potent on paper
If we take away the injury concerns, the 49ers are set up for a successful season.
Last year’s belly flop gave San Francisco the softest schedule in the land, and the NFC West is in a weird spot, as Los Angeles, Seattle, and Arizona also have their bugaboos.
Robert Saleh returns to the Bay Area to run this defense after his disastrous run in New York. Kyle Shanahan’s playbook always has a few tricks up its sleeve, and some late offseason moves bolstered the skill positions, bringing in WR Skyy Moore and RB Brian Robinson Jr.
What will win bets: Offense
Bookmakers are stacking the spreads high versus San Francisco this season.
There are 10 games with lines on the wrong side of a field goal, and six of those sit at -5.5 or higher. The Niners will need points if they’re going to avoid last year’s ATS sorrows.
Brock Purdy’s improbable story scored “Mr. Irrelevant” $265 million this spring, which means the pressure is on to maintain his analytics-friendly play. Even in a down 2024 season, Purdy was a Top 10 QB in many advanced metrics.
Christian McCaffrey played just four games last year, and reports out of 2025 camp are positive. That didn’t stop the team from trading for Robinson right before the season. Both can do damage on the ground and through the air.
The receiving corps is topped by Brandon Aiyuk and TE George Kittle, which is more than most passing games bring to the table. The suspension of Demarcus Robinson (three games) prompted the trade for Moore, and Jauan Jennings led the team in targets last season.
What will lose bets: Defense
Six defensive starters bailed this offseason, leaving Saleh to plug and play around his superstars. Nick Bosa and Fred Warner go a long way in lifting up everyone around them, but they can’t do it all.
The secondary is unsettled, and the defensive front got bullied by opposing rushing attacks, rating 29th in EPA allowed per handoff and 25th in opponent success rate per run. The 49ers couldn’t get rival offenses off the field (25th in third down defense), and they rolled out the red carpet in the red zone (second-worst TD% allowed).
San Francisco failed to cover in a dozen games in 2024, allowing more than 21 points in nine of those ATS duds.
San Francisco 49ers schedule + spot bet: Survive and thrive
The strength of schedule ratings give San Francisco the weakest slate of opponents in 2025. That metric is tempered by a very welcoming home stretch — if the 49ers can get to Week 12 in one piece.
San Fran opens with back-to-back road games and plays six of its first nine contests on the road, including cross-country hikes to New Orleans, Tampa Bay, and New York. All in all, the Niners travel the fifth most miles in 2025 but do get a rest advantage of nine days, according to Sharp Football Analysis.
A Monday night game versus Carolina in Week 12 kicks off a final turn that sees them laying -3 or more in its final six games (with a much-needed bye in Week 14).
The 49ers will host Carolina, Tennessee, Chicago, and Seattle, and travel to Cleveland and Indianapolis to close out the 2025 season. Plenty of winnable matchups could march the 49ers to the top of the NFC West and into the playoffs.
Spot bet: Week 9 at N.Y. Giants -3.5, 44.5
The Niners go to East Rutherford in early November to cap off that grueling road run mentioned above. The 49ers will be playing back-to-back away games and their fourth road stop in five weeks in Week 9.
Whatever is left of San Francisco will also deal with a tricky situational sandwich spot. The team is coming off a big non-conference clash at Houston (and former DC DeMeco Ryans) in Week 8, and they could get caught looking past the pesky Giants to an important home date versus the Rams in Week 10.
Last year’s Niners were 1-4 ATS as road chalk and gave the G-Men the hook on the field goal in Week 9.
Rock out with your Brock out
| Market | |
|---|---|
| Win MVP | +2800 |
| Lead NFL in passing yards | +1500 |
| Over 3850.5 passing yards | -110 |
| Under 3850.5 passing yards | -110 |
| Over 24.5 passing touchdowns | +100 |
| Under 24.5 passing touchdowns | -130 |
Brock Purdy best bet: Over 3850.5 passing yards (-110)
Game managers don’t make $265 million, and Purdy is going to have to prove that in 2025.
Since starting his remarkable story in the NFL, Purdy rates among the elite QBs in many advanced passing stats, including No. 1 in EPA + CPOE and success rate per dropback since 2022.
He finished with 3,864 passing yards in 2024 despite missing a ton of weapons and missing two games. Purdy still has options in CMC, Aiyuk, and Kittle, and he faces a schedule littered with dog-sneeze defenses.
Season-long models all come in way above this passing yard prop, with projections ranging from 4,300 to 4,500-plus.
San Francisco 49ers trend: Divisional Round Overs
The 49ers pack a lot of points in their suitcases whenever they hit the road to play a divisional foe.
San Francisco was 3-0 Over/Under in NFC West road games in 2024, improving the team to 14-8-1 O/U in divisional road games since Kyle Shanahan took over as head coach in 2017.
San Francisco 49ers divisional road games
- Week 1 at Seattle 45.5
- Week 5 at L.A. Rams (TNF) 47.5
- Week 11 at Arizona 47.5
More NFL team previews
Want to see Jason's forecast for the rest of the NFL? Check out all of his NFL team previews below!
| Bills | Ravens | Texans | Broncos |
| Dolphins | Bengals | Colts | Chiefs |
| Patriots | Browns | Jaguars | Raiders |
| Jets | Steelers | Titans | Chargers |
| Cowboys | Bears | Falcons | Cardinals |
| Giants | Lions | Panthers | Rams |
| Eagles | Packers | Saints | 49ers |
| Commanders | Vikings | Buccaneers | Seahawks |
Odds are correct at the time of publishing and are subject to change.
Not intended for use in MA.
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