San Francisco 49ers Betting Odds

Last Updated on October 21, 2025 7:42 am by Henry

Team Overview

The San Francisco 49ers look to bounce back after a 6-11 collapse in 2024. With Brock Purdy still leading the offense, Kyle Shanahan’s squad is healthy and refocused. A favorable schedule makes them divisional favorites.

Offensive Line Analysis

The O-line remains a concern, but returning starters add continuity. Rookie depth will need to step up.

Defensive Line Analysis

The 49ers’ defensive line is strong, but offseason departures raise questions about depth. Nick Bosa remains the star centerpiece.

Week 1 – vs. Seattle Seahawks

Result & Key Stats
The San Francisco 49ers earned a 21–17 road win. QB Brock Purdy threw for 214 yards with 1 TD and 2 INTs, bouncing back in the clutch. The defense held Seattle to just 289 total yards while forcing two turnovers.

Key Moments & Injuries
Purdy connected with TE Jake Tonges for the go-ahead fourth-quarter touchdown. DE Nick Bosa applied relentless pressure—registering a sack and two QB hits. TE George Kittle exited early with a minor groin issue and remains questionable for Week 2.

Looking Ahead
San Francisco travels to face the New Orleans Saints next. Ball security from Purdy and Kittle’s health will be key to sustaining momentum.

Week 2 – vs. New Orleans Saints

Result & Key Stats
The San Francisco 49ers fell 24–10 in New Orleans. QB Brock Purdy threw for 216 yards and 1 TD, but the offense was shut out in the second half.

Key Moments & Injuries
WR Brandon Aiyuk caught the lone touchdown, while TE George Kittle was limited with a lingering groin injury. DE Nick Bosa managed one sack, but the defense couldn’t contain WR Chris Olave.

Looking Ahead
The San Francisco 49ers host the Arizona Cardinals in Week 3 for a divisional clash.

Week 3 – vs. Arizona Cardinals

Result & Key Stats
The San Francisco 49ers edged Arizona 16–15 to stay unbeaten. WR Ricky Pearsall starred (8 catches, 117 yards), including a clutch fourth-down grab from QB Mac Jones to set up SF’s lone TD. RB Christian McCaffrey contributed on the game-winning march.

Key Moments & Injuries
After conceding a late safety, San Francisco drove for the winning kick, with Pearsall converting multiple chain-movers. The 49ers leaned on depth with injuries in the receiving corps.

Looking Ahead
The San Francisco 49ers travel to face the Jacksonville Jaguars in Week 4, with Pearsall’s emerging WR1 role and McCaffrey’s consistency central to the game plan.

Week 4 – vs. Jacksonville Jaguars

Result & Key Stats
The San Francisco 49ers fell 26–21 at home, dropping to 3–1. QB Mac Jones threw for 212 yards and 1 TD, but also tossed a late interception.

Key Moments & Injuries
The Jaguars scored the go-ahead TD midway through the 4th quarter. WR Ricky Pearsall had 6 receptions for 82 yards, while RB Christian McCaffrey added 97 scrimmage yards.

Looking Ahead
The 49ers travel to face the Los Angeles Rams in Week 5.

Week 5 – vs. Los Angeles Rams

Result & Key Stats
The San Francisco 49ers edged their division rivals 26–23 in a tense battle at SoFi Stadium. QB Mac Jones put together one of his strongest performances of the year, throwing for 342 yards on 33-of-49 passing with 2 touchdowns and no interceptions. Despite a limited rushing attack that generated only 74 total yards, San Francisco leaned heavily on its passing game. WR Kendrick Bourne led the receiving corps with 142 yards, while RB Christian McCaffrey chipped in with 82 yards and a receiving touchdown.

Key Moments & Injuries
The 49ers controlled the clock late, with Jones connecting on key throws to extend drives. TE Jake Tonges added a touchdown that gave San Francisco breathing room before the Rams rallied. Defensively, LB Fred Warner continued his dominance with 12 tackles, while pass rusher Bryce Huff notched a critical sack to slow Matthew Stafford’s comeback attempt. Injuries remain a concern, as WR Ricky Pearsall (knee) and WR Jauan Jennings (rib/ankle) were both ruled out, and QB Brock Purdy (toe) also missed the contest, leaving Jones to shoulder the load.

Looking Ahead
San Francisco heads to Tampa Bay in Week 6 for a massive NFC clash against the Buccaneers. With the offense showing resilience and Jones finding rhythm with his receivers, the 49ers will need to protect him against Tampa’s fierce pass rush. McCaffrey’s role as a dual threat will once again be vital, especially with multiple wideouts still battling injuries.

Week 6 – vs. Tampa Bay Buccaneers

The San Francisco 49ers dropped to 4–2 after a tough 30–19 road loss against Tampa Bay. Mac Jones had an inconsistent outing—throwing for 347 yards but also two interceptions while facing heavy pressure (six sacks). Christian McCaffrey fought for 111 total yards and a rushing touchdown, but the offense struggled to convert red-zone chances into points. Kendrick Bourne led all receivers with 142 yards, yet turnovers and protection breakdowns proved costly.

Defensively, the 49ers’ front seven couldn’t slow down Baker Mayfield’s rhythm. While Marvin Williams and Myles Huff registered key stops, Tampa’s explosive plays through the air tilted momentum early. Eddy Piñeiro was automatic, hitting all four of his field goals—including a 54-yarder—but the lack of offensive balance kept San Francisco chasing the scoreboard.

Looking Ahead: The 49ers will regroup before returning home to face the Atlanta Falcons. With several starters listed as questionable—like Brock Purdy and Yetur Gross-Matos—San Francisco’s focus will be on shoring up protection and cleaning up mental errors to stay competitive in the NFC West.

Week 7 – vs. Atlanta Falcons

The San Francisco 49ers secured a steady 20–10 road win over the Atlanta Falcons, leaning on a vintage performance from Christian McCaffrey, who totaled 201 scrimmage yards (129 rushing, 72 receiving) and two rushing touchdowns. His versatility powered an offense that controlled the pace and wore down Atlanta’s defensive front. Quarterback Mac Jones managed the game efficiently, completing 17 of 26 passes for 152 yards, while Jauan Jennings and Skyy Moore combined for key third-down conversions.

Defensively, the 49ers contained the Falcons’ running game and forced one fumble. Bryce Huff and Samson Okuayinonu each recorded sacks, while Deommodore Lenoir anchored the secondary with tight coverage throughout. Despite allowing over 240 passing yards, San Francisco’s defense tightened in the red zone, limiting Atlanta to just one touchdown.

Looking Ahead: Now 6–2, the 49ers continue to assert themselves as NFC contenders. With McCaffrey in peak form and the defense regaining its identity, San Francisco will look to carry this balance into next week’s matchup — where they’ll aim to extend their winning streak and solidify their hold atop the NFC West.

Odds to Win Division & Super Bowl

• Division Odds: +160
  
• Super Bowl Odds: Top-5 contender at +1200
  

Predictions

The 49ers should reclaim the NFC West title. Predicted record: 11-6, playoff berth expected.