The San Francisco 49ers and Arizona Cardinals meet this Sunday in Week 11 for their second matchup of the season. In the first meeting, the 49ers won 16-15 on an Eddie Piñeiro field goal as time expired. Here is a look at the history of this matchup and which team has the edge in the rivalry.
San Francisco Looks To Extend Historic Lead Against The Arizona Cardinals
The rivalry between the Cardinals and 49ers truly intensified in 2002, when Arizona joined the NFC West during the league’s divisional realignment. Before that, the Cardinals were part of what is now the NFC East, alongside the Dallas Cowboys, Philadelphia Eagles, Washington’s franchise at the time, and the New York Giants.
Since entering the NFC West, the matchups between the two teams have been consistently competitive, with each side experiencing stretches of dominance. The 49ers went four years without beating Arizona between 2015 and 2018, a period marked by losing seasons and low competitiveness for San Francisco.
Between the 2022 and 2023 seasons, the script flipped. The 49ers swept the Cardinals twice, including an international game in Mexico in 2022. The 2023 matchups were completely one-sided, highlighted by standout performances from Christian McCaffrey, who scored seven touchdowns across the two games.
For the next game, all eyes are once again on McCaffrey for a big performance. He earned a C- grade in his first matchup against the Cardinals according to the PFSN RB Impact Meter, but he came through in the clutch late in the game to help set up the decisive field goal and finished the day with 140 total yards.
Historically, San Francisco holds the edge in the rivalry, with 37 wins to Arizona’s 31. The first chapter of the 2025 season went to the 49ers, led by Mac Jones at quarterback while Brock Purdy was still recovering from injury.
In this Sunday’s game, Purdy returns to the lineup, while Jacoby Brissett starts for the Cardinals in place of the injured Kyler Murray, who played in the first meeting. A victory would move San Francisco to 4-1 in the division and set up a potentially decisive Week 18 matchup against the Seattle Seahawks for the division title.
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In the game preview, the 49ers are expected to come out on top, beating the Cardinals 30 to 21. The major difference heading into this matchup is that San Francisco finally has its full offensive unit available for the first time this season, with Purdy, Pearsall, George Kittle, Jauan Jennings, and McCaffrey all ready to go.
Arizona enters the game dealing with several key absences, including wide receiver Marvin Harrison Jr., linebackers Mack Wilson and Baron Browning, and cornerback Will Johnson.
