- Matchup: Arizona Cardinals vs San Francisco 49ers
- Event Date: Sunday, September 21, 2025
- Venue: Levi’s Stadium, Santa Clara, CA
- Broadcast: FOX
- Betting Odds: 49ers favored by 1.5 points
- Over/Under Total: 43.5
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On Sunday, the San Francisco 49ers (2-0) will host the Arizona Cardinals (2-0) at Levi’s Stadium. Arizona enters this contest as 1.5-point underdogs according to betting lines, with a total over/under set at 43.5 points.
The Arizona Cardinals are currently enjoying a flawless record of 2-0 this season. In their latest game, the Cardinals triumphed over the Carolina Panthers, securing a 27-22 victory. James Conner was instrumental in the run game, carrying the ball 11 times for 34 yards (averaging 3.1 yards per carry). Trey McBride made a notable contribution, racking up 78 yards on six receptions, averaging 13.0 yards per catch. Quarterback Kyler Murray completed 17 of 25 passes for 220 yards and one touchdown, finishing with a QB rating of 92.1, while unfortunately throwing one interception. The Cardinals’ defense held the Panthers to 49 rushing yards on 19 carries, yielding an average of 2.6 yards per rush. In the passing game, Arizona allowed 35 completions on 55 attempts, resulting in a total of 303 yards and a completion rate of 63.6%. Overall, the Cardinals executed 47 plays, accumulating 293 total yards. On the ground, Arizona attempted 22 rushes, producing 82 yards for an average of 3.7 yards per attempt.
In terms of scoring, the Cardinals average 23.5 points per game. They also run for an average of 114.0 yards per contest, placing them 13th in the NFL. Currently, Arizona has recorded 569 total yards, along with 21 first downs this season. They have incurred 21 penalties leading to 150 yards lost and have turned the ball over once. In terms of touchdowns, Arizona has scored 3 via passing and 1 on the ground.
Defensively, the Cardinals have allowed 511 passing yards, ranking 26th in the league. They surrender approximately 255.5 yards per game through the air with a completion percentage of 61.4%. Against the run, they have given up a total of 156 yards through two games, allowing 3 rushing touchdowns and 1 passing touchdown. Overall, Arizona yields an average of 333.5 yards per game, ranking 21st in the NFL, while allowing 3.8 yards per carry and 78 rushing yards per game. Surprisingly, the Cardinals rank 10th in the league for points allowed, limiting opponents to 17.5 points per game.
The San Francisco 49ers also boast a perfect 2-0 season record. In their last outing, the 49ers secured a narrow 26-21 victory against the New Orleans Saints. Mac Jones showcased an impressive performance, tossing 3 touchdowns and finishing with 279 yards on 26 completions out of 39 attempts, achieving a QB rating of 113.1 with no interceptions. Christian McCaffrey was pivotal in the run game, carrying the ball 13 times for 55 yards at an average of 4.2 yards per carry. Jauan Jennings excelled in receiving, catching 5 passes for a total of 89 yards, averaging 17.8 yards per reception. The 49ers managed 77 rushing yards on 26 carries, averaging 3.0 yards per attempt, while accumulating 344 total yards from 65 plays with an average of 5.3 yards per play. On the defensive side, San Francisco’s secondary allowed a completion percentage of 73.5%, giving up 186 yards on 25 completions from 34 attempts. They also permitted 121 yards on 30 rushing attempts, averaging 4.0 yards per carry.
When evaluating their scoring capability, the 49ers rank 18th in the league, averaging 21.5 points per game. To date, they have amassed 532 passing yards, with an average of 266.0 passing yards per game, placing them 6th in the NFL. In terms of rushing, they average 98.0 yards per game, having accumulated a total of 196 rushing yards. Overall, San Francisco averages 364.0 yards per game, ranking 8th in the league. The offense has accrued 14 penalties resulting in 101 yards lost, ranking them 17th in helping the opposition. They have successfully recorded 30 first downs so far.
Defensively, the 49ers allow an average of 17.0 points per game, placing them 7th in the NFL. They have permitted 3 touchdown passes and an average of 166.0 passing yards per game, ranking 6th in the league. In terms of rushing defense, the 49ers have allowed a total of 205 yards, averaging 102.5 rushing yards per game, including 1 rushing touchdown. The defense has been active on the field for 117 plays from scrimmage, ranking them 10th in the league, and they have created 3 turnovers, yielding a total of 34 points.
Who will cover the spread in this pivotal Cardinals-49ers matchup?
Recommended Pick: Bet on the 49ers -1.5
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