Betting Trends Arizona Cardinals vs San Francisco 49ers

The upcoming Sunday football game on November 16, 2025, between the Arizona Cardinals and the San Francisco 49ers at State Farm Stadium in Glendale, AZ, is set to be an exciting NFL Week 11 matchup. The Cardinals will start backup quarterback Jacoby Brissett, as the usual starter Kyler Murray remains on injured reserve with a mid-foot sprain. Despite this, Brissett's experience should help maintain offensive stability. The 49ers will have Brock Purdy under center, who has shown solid performances this season.

Arizona's offense averages 316.3 total yards per game, with a balanced attack of 202.9 passing yards and 113.4 rushing yards. Their defense allows 339.4 total yards, with a slight vulnerability to the pass, conceding 225.3 passing yards on average. San Francisco's offense is more pass-heavy, averaging 261.4 passing yards and 94.8 rushing yards per game. Their defense is strong, allowing only 339.4 total yards with a solid pass rush that has sacked opponents 7.7 times for 48.5 yards.

The Cardinals have a 5-4-0 record against the spread (ATS), while the 49ers are 5-5-0 ATS. The 49ers are favored by 3.5 points with a total points line set at 48.5. This suggests a moderately close game with a high scoring potential. The 49ers' stronger pass protection and pass rush could give them an edge over Arizona's balanced offense and slightly weaker pass defense.

Key injuries to watch include Arizona's questionable offensive linemen Will Hernandez and Kelvin Beachum, which could impact pass protection. San Francisco's defense is missing star linebacker Fred Warner due to injury, which might affect their run defense. The game will be broadcast on FOX, offering fans a chance to catch the action live.

In their last matchup on September 21, 2025, the 49ers edged out the Cardinals 16-15 in a tightly contested game, which underlines how close these teams can be. The betting trends and game insights suggest considering the 49ers to cover the spread, given their home advantage and stronger defensive front. For bettors looking to maximize their edge, Start your OddsTrader Turbo subscription or place your bet with a U.S. regulated sportsbook like Caesars.