The Arizona Cardinals travel to Levi’s Stadium in Santa Clara, California on Sunday, September 27, 2026, to face the San Francisco 49ers at 4:05 p.m. ET. San Francisco enters the game 2-0 after beating Miami in Week 2, while Arizona is 1-1 following a 31-7 loss to Seattle. The 49ers are favored by 8.5 points.
San Francisco is averaging 31 points and 380.5 yards per game and ranks among the league’s best on third down. Quarterback Brock Purdy has not been sacked through the first two games, the cleanest start to a season in franchise history, and has thrown for 492 yards and 5 touchdowns. Arizona’s defense has allowed 22.5 points per game, putting pressure on Purdy to convert drives into points rather than just yardage.
San Francisco’s defense has been just as strong, allowing only 10 points per game, third-fewest in the league, along with 4 sacks through two contests. Running back Christian McCaffrey reached 100 career regular-season touchdowns during the win over Miami, scoring twice from a yard out. He finished that game with 10 carries for 23 yards and 4 catches for 43 yards, and the 49ers are now averaging 134.5 rushing yards per game with 3 rushing touchdowns on the season. Arizona has given up 6 total touchdowns on defense through two games.
Arizona averages 16.5 points per game, with 179 passing yards and 93 rushing yards per game. Quarterback Jacoby Brissett has thrown for 372 yards and 2 touchdowns this season but managed just 95 yards passing, along with an interception, in last week’s loss to Seattle. He’ll face a San Francisco front that already has 4 sacks in two games.
Tight end Trey McBride has been Arizona’s most consistent offensive weapon, catching 17 of 22 targets for 136 yards and 2 touchdowns, scoring in both of the Cardinals’ first two games, including 8 catches for 41 yards against Seattle. Against a 49ers defense allowing just 10 points per game, McBride’s underneath targets may be one of the few reliable ways Arizona can sustain drives.
Arizona does carry one statistical edge into the matchup: a plus-2 turnover margin, built largely by its defense forcing takeaways rather than by production from Brissett through the air. Holding onto that margin will be important against a 49ers defense that already has the Cardinals’ quarterback at a disadvantage.
