The Arizona Cardinals will play the San Francisco 49ers on Sunday, September 21, 2025. The game will take place at Levi’s Stadium in Santa Clara, CA, with kickoff set for 4:25 PM. Fans can catch the action on FOX.

Cardinals vs. 49ers Betting Prediction

• Money Line Prediction: Arizona Cardinals +106. The Cardinals have a strong start to the season with a 2-0 record. They also have a solid road performance, winning their only away game so far.
• Over/Under Prediction: Under 44.0. Both teams have shown strong defenses, with the Cardinals allowing 22 and 13 points in their first two games, while the 49ers allowed 21 and 13 points.

Team Trends

• The Arizona Cardinals have started the season with a 2-0 record, winning both home and away games.
• San Francisco 49ers also have a 2-0 record this season, winning both games on the road.
• Arizona Cardinals’ head coach is Jonathan Gannon, while the 49ers are led by Kyle Shanahan.
• In their last game, the Cardinals won against the Carolina Panthers with a score of 27-22.
• The 49ers’ last victory was against the New Orleans Saints, ending with a score of 26-21.

Cardinals vs 49ers Preview

The Arizona Cardinals and the San Francisco 49ers both enter this Week 3 game with perfect 2-0 records. The 49ers have shown strong performances on the road, and now they get to play at home in Levi’s Stadium. The Cardinals have also been solid, winning both of their games. This game will be a test for both teams as they aim to stay unbeaten.

Kyler Murray leads the Cardinals with a projected 215 passing yards and over one touchdown. On the other side, Mac Jones is expected to throw for 215.8 yards and a bit more than one touchdown for the 49ers. Both teams have strong running backs, with Christian McCaffrey expected to gain 82.9 rushing yards for the 49ers and James Conner projected for 62.7 rushing yards for the Cardinals. This game could be a close one with these key players on the field.

49ers Ready to Defend Home Turf

The San Francisco 49ers are led by head coach Kyle Shanahan. They have started the season strong with a 2-0-0 record. The team plays their games at Levi’s Stadium and is part of the NFC West division.

The 49ers have several standout players this season. Mac Jones, the quarterback, is expected to throw for 215.8 yards with 1.4 touchdowns in the upcoming game. Christian McCaffrey is another key player, with a projection of 82.9 rushing yards and 4 receptions.

San Francisco’s team offense ranks high in passing yards and first downs. Last season, they ranked 4th in passing yards with 4,234. On defense, they held their opponents to an 8th-ranked 5,396 offensive yards.

Cardinals Look to Extend Winning Streak

The Arizona Cardinals, led by head coach Jonathan Gannon, have a perfect 2-0-0 record this season. They have shown strength both at home and on the road, playing their games at State Farm Stadium. Their offense ranks 18th in passing yards and 7th in rushing yards from last season.

Kyler Murray is the top quarterback, with 383 passing yards and 3 touchdowns in two games. He is expected to throw for 215.0 yards and 1.3 touchdowns in the next game. James Conner, a key running back, has 73 rushing yards and 1 touchdown this season.

Marvin Harrison Jr. is a leading wide receiver with 98 receiving yards and 1 touchdown in two games. The tight end Trey McBride has 12 receptions and 139 receiving yards. Chad Ryland, the kicker, has made 4 field goals this season and scored 19 fantasy points.

Final Betting Pick

The Arizona Cardinals have a strong start to the season with a 2-0 record. They have shown they can perform well on the road, winning their only away game so far. Kyler Murray is projected to throw for 215 yards and has been consistent with his performance. This makes the Cardinals a good pick for the money line at +106.

Both teams have strong defenses, which supports the under 44.0 prediction. The Cardinals have allowed only 22 and 13 points in their first two games. The 49ers have also shown a solid defense, allowing 21 and 13 points. With both teams focusing on defense, the total score is likely to stay under 44 points.

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All odds are courtesy of Action247 Sportsbook. Good luck!!

* All odds are provided by Action247 Sportsbook and all odds subject to change. **All views expressed are my own. My picks are my own and are not a guarantee, bet at your own risk. Action247 does not warrant the accuracy of completeness of the information, text, graphics, links or other items contained within these post.