Arizona Cardinals vs San Francisco 49ers Betting Trends

The upcoming NFL showdown on November 16, 2025, between the San Francisco 49ers and the Arizona Cardinals at State Farm Stadium in Glendale, AZ, promises to be a thrilling Sunday football event. The 49ers, led by starting quarterback Brock Purdy, face off against the Cardinals, who will rely on backup quarterback Jacoby Brissett due to Kyler Murray's injury. This game is pivotal in Week 11 of the 2025-26 NFL season and will be broadcast on FOX, offering fans and bettors an exciting opportunity to engage with the sport.

Betting trends indicate the 49ers as favorites with a -3 point spread and odds of -122 at Caesars, while the Cardinals are +3 underdogs at +102. The total points line is set at 48.5 with an under favorite at -112, suggesting a moderately high-scoring game. The 49ers boast a strong passing offense averaging 261.4 yards per game, matched against the Cardinals' solid pass defense allowing 225.3 passing yards. Meanwhile, the Cardinals' rushing offense is slightly more productive than the 49ers', but San Francisco's rush defense is stout, allowing just 110.6 rushing yards per game.

Key injuries for the Cardinals include questionable statuses for offensive linemen Will Hernandez and Kelvin Beachum, and running back Zonovan Knight, which could impact pass protection and rushing efficiency. The 49ers are missing linebacker Fred Warner and defensive lineman Nick Bosa, potentially weakening their pass rush and run defense. These factors could influence the game's pace and scoring opportunities.

Recent performances show the 49ers with a 6-4 straight-up record and 5-5 against the spread, while the Cardinals hold a 3-6 record straight up and 5-4 against the spread. Both teams have shown tendencies to stay under the total points line in recent games, making the under a tempting betting insight. The 49ers have a slight advantage in home and away records, adding to their edge in this matchup.

For bettors, analyzing these betting trends alongside game insights on quarterback play, offensive and defensive matchups, and injury impacts will be crucial. The 49ers' stronger passing game and home advantage make them a smart pick to cover the spread, but the Cardinals' resilience and home crowd could keep the game tight. Ready to bet smarter? Start your OddsTrader Turbo subscription now or place your bet with a U.S. regulated sportsbook and profit off the edge.

In their last matchup on September 21, 2025, which the 49ers won 16-15, the San Francisco 49ers narrowly defeated the Arizona Cardinals in a closely contested game that went under the total points line.