San Francisco 49ers 2025 Schedule, Odds & Predictions: AI Picks for Every Game

We're breaking down everything you need to know about the 49ers, including odds and projections for all 17 games.

Last updated: May 15, 2025 8:29 AM EDT • 4 min read

San Francisco 49ers 2025 Schedule: Game-by-Game Odds, Predictions & AI Picks — Pictured: San Francisco 49ers running back Christian McCaffrey rushes the ball against the Seattle Seahawks. Photo by David Gonzales / Imagn Images.

We're breaking down the San Francisco 49ers schedule, odds, and predictions for the 2025 NFL season following the official schedule release. The 49ers are projected to win 10.5 games across our best sports betting sites, and we're offering our 2025 win-loss predictions with AI picks for all 17 games.

📅 San Francisco 49ers 2025 schedule & odds for every game

Odds via DraftKings as of Thursday, May 15. All times listed in Eastern Time.

Week	Date	Opponent	Favorite
1	Sunday, Sept. 7 @ 4:05 PM	at Seahawks	49ers -1.5
2	Sunday, Sept. 14 @ 1 PM	at Saints	49ers -7
3	Sunday, Sept. 21 @ 4:25 PM	vs. Cardinals	49ers -3.5
4	Sunday, Sept. 28 @ 4:05 PM	vs. Jaguars	49ers -5.5
5	Thursday, Oct. 2 @ 8:15 PM	at Rams	Rams -1.5
6	Sunday, Oct. 12 @ 1 PM	at Buccaneers	Buccaneers -1.5
7	Sunday, Oct. 19 @ 8:20 PM	vs. Falcons	49ers -6.5
8	Sunday, Oct. 26 @ 1 PM	at Texans	49ers -1.5
9	Sunday, Nov. 2 @ 1 PM	at Giants	49ers -3.5
10	Sunday, Nov. 9 @ 4:25 PM	vs. Rams	49ers -1.5
11	Sunday, Nov. 16 @ 4:05 PM	at Cardinals	49ers -1.5
12	Monday, Nov. 24 @ 8:15 PM	vs. Panthers	49ers -7
13	Sunday, Nov. 30 @ 1 PM	at Browns	49ers -6
14	BYE WEEK	-	-
15	Sunday, Dec. 14 @ 4:25 PM	vs. Titans	49ers -7.5
16	Monday, Dec. 22 @ 8:15 PM	at Colts	49ers -3
17	Sunday, Dec. 28 @ 8:20 PM	vs. Bears	49ers -3.5
18	TBD	vs. Seahawks	49ers -4.5

👉 Check out the full 2025 NFL schedule with odds for every game.

📊 San Francisco 49ers odds to win Super Bowl & best futures bets

🔎 Our NFL player prop odds tool can help you find the best NFL odds across legal sportsbooks in your area!

💰 San Francisco 49ers O/U win total

Latest NFL win totals via BetMGM as of Thursday, May 16.

Over 10.5 wins: +110 (bet $10 to win $11)
Under 10.5 wins: -130 (bet $10 to win $7.69)

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Each product featured on our website has been meticulously researched and selected by our team of experts. If you sign up through our links, we may get a commission.

🔮 San Francisco 49ers 2025 predictions: Game-by-game picks & final record

Check out our 2025 NFL season predictions for projected standings, playoff results, and award winners - and a breakdown of how our AI model predicts every game.

🤖 San Francisco 49ers 2025 AI projections

Week 1: 49ers 27, Seahawks 24 ✅
Week 2: 49ers 34, Saints 17 ✅
Week 3: 49ers 34, Cardinals 20 ✅
Week 4: 49ers 31, Jaguars 23 ✅
Week 5: 49ers 30, Rams 23 ✅
Week 6: 49ers 28, Buccaneers 26 ✅
Week 7: 49ers 33, Falcons 24 ✅
Week 8: Texans 31, 49ers 28 ❌
Week 9: 49ers 30, Giants 16 ✅
Week 10: Rams 34, 49ers 31 ❌
Week 11: 49ers 33, Cardinals 20 ✅
Week 12: 49ers 30, Panthers 21 ✅
Week 13: Browns 30, 49ers 13 ❌
Week 15: 49ers 30, Titans 14 ✅
Week 16: 49ers 31, Colts 27 ✅
Week 17: 49ers 33, Bears 20 ✅
Week 18: 49ers 27, Seahawks 20 ✅

🏈 San Francisco 49ers 2025 record prediction

Projected win-loss record: 14-3

🔮 2025 NFL season previews & predictions

Following the NFL schedule release, we broke down the odds for every game and asked AI to predict every game (and more). Below are our team-by-team schedules, odds, and predictions for Week 1 through Week 18.

Buffalo Bills	Miami Dolphins	New York Jets	New England Patriots
Baltimore Ravens	Pittsburgh Steelers	Cincinnati Bengals	Cleveland Browns
Houston Texans	Indianapolis Colts	Jacksonville Jaguars	Tennessee Titans
Kansas City Chiefs	Los Angeles Chargers	Denver Broncos	Las Vegas Raiders
Philadelphia Eagles	Washington Commanders	Dallas Cowboys	New York Giants
Detroit Lions	Minnesota Vikings	Green Bay Packers	Chicago Bears
Tampa Bay Buccaneers	Atlanta Falcons	Carolina Panthers	New Orleans Saints
Los Angeles Rams	Seattle Seahawks	Arizona Cardinals	San Francisco 49ers

💵 Best NFL betting sites

Ready to bet on the NFL this season? Check out our best NFL betting sites and the best sportsbook promos for the 2025-26 NFL season:

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Each betting site featured on SBR has been meticulously researched and selected by our team of experts. If you sign up through our links, we may get a commission.

Written By:
C Jackson Cowart

C Jackson Cowart is a publishing editor and lead writer for Sportsbook Review. An award-winning writer, reporter, and editor with a decade of sports media experience, "C-Jax" has worked with ESPN, Forbes, theScore, and various daily newspapers before joining the Sportsbook Review team. He's a proud graduate of the University of North Carolina, where he served as a beat writer for the Tar Heels' championship run through the NCAA men's basketball tournament in 2017. Jackson has spent the last five years covering sports betting as a predictive analyst, features writer, and industry reporter. Since joining the team in 2023, he's played a key role in Sportsbook Review's coverage of the Super Bowl, March Madness, and NBA playoffs while serving as the lead writer for the growing WNBA and NASCAR betting scenes. Though he's cashed some big bets over the years -- including Lamar Jackson to win MVP (twice) -- he's still haunted by enough second-place bet slips to wallpaper his home office. While Jackson is a committed "process over results" bettor with a keen eye for advanced stats and subtle bias in futures markets, he also embraces sports betting as a vehicle for entertainment and personal investment. He's written about everything from hot dogs to groundhogs and still hasn't forgiven his "inside source" for a sabotaged bet on the Gatorade color in Super Bowl LV.