San Francisco 49ers @ Arizona Cardinals 11/16/2025
San Francisco rolls into the desert for a late-afternoon NFC West clash at State Farm Stadium on Sunday, November 16, 2025 (4:05 p.m. ET). It’s a divisional rivalry with plenty of betting intrigue and a few moving parts on the lineup front. Through 10 games, San Francisco has averaged 22.0 points per game while allowing 23.0, and they’ve traveled well with roughly 22.8 points scored and allowed per road contest. Arizona, at 3-6 through nine, is right around 22.4 points per game and giving up 23.9, with a comparable home profile: about 22.8 scored and 23.5 allowed in Glendale. In short, both teams hover near league-average scoring with slight defensive leaks.
Recent form leans San Francisco’s way (2-3 in the last five) compared to Arizona (1-4), though the Cards were chippy ATS last year and have continued showing punch as home underdogs. The last direct meeting went 16-15 to San Francisco in a grinder, and that game script hangs over this number. With the dome, weather isn’t a factor. Execution and red zone efficiency will be.
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Our betting predictions for the match San Francisco 49ers @ Arizona Cardinals
Main Tip: Game Total Under 49.5 Points
Our primary betting prediction — Game Total Under 49.5 points (Best odds: -125 at BetMGM): This number sits a tick high relative to each team’s season-long scoring averages and what we’ve seen from their NFC West profile. San Francisco is right at 22.0 per game, Arizona just above 22, and both are allowing in the low-to-mid 20s. Divisional familiarity tends to compress possessions. In a controlled dome environment, drive consistency matters, but neither side projects to explode. The Under 49.5 at -125 with BetMGM is our preferred angle.
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Tip 2: Moneyline – San Francisco 49ers
Our second prediction — Moneyline: San Francisco 49ers (Best odds at DraftKings): The 49ers have traveled well, with roughly 22.8 points per game on the road while playing opponents almost even on the scoreboard away from home. They’ve taken three of the last five head-to-head and remain more stable offensively when they avoid turnovers. Even with lineup questions, their structure under Kyle Shanahan, plus a better recent five-game baseline than Arizona, nudges us toward San Francisco’s ML at DraftKings.
Tip 3: Spread – Arizona Cardinals +3.0
Our final betting tip — Spread: Arizona Cardinals +3.0 (Best Odds: -115 at DraftKings): If you prefer grabbing points with a home dog, the Cardinals at +3.0 come with a strong case. Arizona has been feisty at home against the number, and divisional matchups often play tight. With the Cards’ scoring and allowing numbers aligning closely with San Francisco’s per-game profile, a field-goal cushion carries real value. Arizona +3.0 at -115 with DraftKings is a sensible alternative or hedge to the moneyline approach.
Team news
The quarterback situation is the headline. San Francisco’s context points to Joshua Dobbs as a potential starter, a familiar face in Arizona after starting eight games there last season. Reported injury notes from earlier in 2025 included Brock Purdy (elbow) and key 49ers skill players like Deebo Samuel (ribs/wrist) managing issues, plus questions around George Kittle (ankle/hamstring). On the defensive side, San Francisco has monitored the secondary, with Deommodore Lenoir and Isaac Yiadom appearing on previous lists.
For Arizona, earlier notes indicated kicker Matt Prater (knee) and depth along the offensive line were concerns, with Jackson Barton out and Kelvin Beachum limited at times. The Cardinals have also navigated wide receiver and linebacker availability, and the backfield was thinned at points with James Conner and Trey Benson previously referenced on IR. Always verify inactive 90 minutes before kickoff, but both staffs have had to patch and shuffle.
Arizona Cardinals performance check
Under Jonathan Gannon, Arizona’s offense has hovered around 22.4 points per game, while the defense has yielded roughly 23.9. At home, they’ve produced about 22.8 and allowed 23.5, signaling tight margins in Glendale. They enter off a 22-44 loss to Seattle, a game that got away defensively. The last five have been a grind (1-4), but the Cards have maintained a betting edge as underdogs in spots, especially within State Farm Stadium’s controlled conditions.
Personnel-wise, Trey McBride has emerged as a focal point, and his Pro Bowl form from earlier in 2025 carried into this season with reliable chain-moving production. Greg Dortch has offered quick-game utility, while the line’s health remains a swing factor for protecting Kyler Murray and establishing any ground rhythm. With the backfield lacking its full complement at stretches, Arizona’s pass game shoulders a bigger share of early-down success. Takeaways and short fields could flip their variance.
How is the current performance of the San Francisco 49ers
Kyle Shanahan’s group is averaging 22.0 points while allowing 23.0, and they’ve held up on the road: roughly 22.8 scored and 22.8 allowed. They’re 2-3 in the last five, most recently taking a 26-42 home loss to the Rams. The offensive framework still creates answers—motions, spacing, and run-pass conflicts—but injuries and quarterback continuity have been the wildcards. If Joshua Dobbs goes, his mobility and familiarity with Arizona’s defense are noteworthy, and Shanahan can scheme to his strengths.
Brandon Aiyuk remains a downfield difference-maker, and rookie Ricky Pearsall has flashed—the 8-catch, 117-yard showing in their 16-15 win over Arizona in 2025 stands out. On defense, pressure players can tilt matchups, but communication in the secondary and tackling angles will be crucial against Murray’s improvisation. San Francisco’s path to covering the ML price is cleaner if they control early downs and avoid giving Arizona free possessions.
Team Statistics
- Scoring averages:
- San Francisco: 22.0 points per game scored; 23.0 allowed. Road splits around 22.8 scored and 22.8 allowed.
- Arizona: 22.4 points per game scored; 23.9 allowed. Home splits about 22.8 scored and 23.5 allowed.
- Recent form:
- Last five: Arizona 1-4; San Francisco 2-3.
- Head-to-head last five: 49ers 3 wins, Cardinals 2 wins.
Keyplayer Statistics/Momentum/External Factors
- Last direct match Arizona Cardinals vs San Francisco 49ers: San Francisco won 16-15—a tight, low-scoring grinder that echoes the case for an Under again if pace and red zone execution mirror that outcome.
- – Performance last 5 matches: Arizona 1 win, 4 losses; San Francisco 2 wins, 3 losses.
- – Last match results: Arizona lost 22-44 at Seattle; San Francisco lost 26-42 at home to the Rams.
- Personnel and momentum:
- Arizona: Trey McBride’s reception surge has anchored the passing game, giving Murray a high-percentage option and YAC threat. When the line holds, the Cards create explosive windows off play-action and scramble drills. Health in the trenches is pivotal to avoid negative plays.
- San Francisco: Aiyuk’s separation skills and Pearsall’s growth can stress Arizona’s secondary. If Dobbs starts, QB run elements and rollout action can simplify reads, move the pocket, and create intermediate throws to Kittle if he’s ready to go.
- External factors: Dome conditions mean no weather risk. Travel is minimal for San Francisco relative to long-haul cross-country trips. Market context has shown Arizona can be frisky against the number at home, while San Francisco’s road framework tends to keep them in control if they avoid giveaways.
- Trend notes:
- Cardinals: 7-3 ATS over their last 10, including 4-1 ATS at home; however, 5-15 ATS in their last 20 vs NFC West opponents.
- 49ers and Cardinals had contrasting ATS profiles last season (49ers 5-11 ATS; Cardinals 10-6 ATS), underscoring the volatility of divisional games.
From divisional rivalries to prime-time thrillers, every game tells a story. See how the oddsmakers are writing it — explore the NFL betting odds for this week’s biggest matchups.
TrustnBet Final Thoughts
We’re leaning toward a controlled, possession-minded game that tilts conservative on the scoreboard. Our three plays reflect that: Under 49.5 at -125 as the favorite pick, 49ers on the moneyline based on structural stability and road profile, and Cardinals +3.0 at -115 as a viable home-dog offset if you want points in your pocket for a divisional scrap. Keep an eye on inactives, but the angles hold even with lineup shuffling.
