The game was a defensive battle for three quarters, with both teams limited to field goals. The 49ers played without starting quarterback Brock Purdy, turning to Mac Jones, while Arizona lost running back James Conner to a significant ankle injury in the third quarter. San Francisco also saw star pass rusher Nick Bosa exit in the first half with a knee issue and not return.
Momentum swung in the fourth quarter. The Cardinals took a late 15-13 lead after defensive lineman Calais Campbell drew a holding penalty in the end zone for a rare safety—Arizona’s first tiebreaking safety in the fourth quarter in nearly 11 years. However, rookie Upton Stout broke up a crucial third-down pass to Zay Jones, forcing Arizona to punt and giving the 49ers one last chance.
Mac Jones, finishing 27-for-41 for 284 yards with a touchdown and an interception, orchestrated a composed final drive, moving the Niners 59 yards in 1:46 to set up Pineiro’s game-winning kick. The Cardinals’ Kyler Murray went 22-for-35 for 159 yards and a touchdown, connecting with tight end Trey McBride for a 1-yard score to tie the game at 13 earlier in the fourth quarter.
Both teams missed scoring opportunities in the third quarter, including a dropped pass by Emari Demercado near the goal line for Arizona and a fourth-down stop by the Cardinals’ defense against Christian McCaffrey.
The win keeps San Francisco (3-0) in first place in the NFC West, while Arizona (2-1) drops its first game of the season. The Cardinals will look to regroup as they host Seattle on Thursday night, while the 49ers prepare to welcome Jacksonville next Sunday.
For a detailed box score and play-by-play, visit 49ers 16-15 Cardinals (Sep 21, 2025) Game Recap. Additional analysis and live updates are available on Arizona Republic’s coverage.