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San Francisco QB Brock Purdy is expected to miss a second straight game as the 49ers (-2.5) host the Arizona Cardinals today. With Mac Jones filling in for Purdy, can the Cardinals (+125) win as underdogs?
Cardinals vs 49ers Predictions - 4:25pm EDT - 9/21
All odds are courtesy of bet365, correct at the time of publishing, and subject to change.
- Kyler Murray 30+ Rushing Yards @ -110 with bet365
- Ricky Pearsall Anytime TD Scorer @ +220 with bet365
- Cardinals ML @ +125 with bet365
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Cardinals vs 49ers Odds
- Spread: 49ers -2.5 (-120)
- Moneyline: Cardinals (+125) 49ers (-150)
- Total: O/U 45.5
Cardinals vs 49ers Picks
Can’t Catch Kyler - Kyler Murray 30+ Rushing Yards (-110)
Arizona Cardinals QB Kyler Murray has had some of his best rushing games against the 49ers over the years. Last season, he broke out for a 50-yard TD run in a 24-23 Week 5 win over the Niners. The 83 rushing yards Murray picked up in that game were his season high.
This season, Murray has carried the ball 14 times for 70 yards. He has reached the 30-yard threshold in both games so far. With six 30-yard rushing games in eight career starts against the 49ers, Murray could have some success on the ground again today.
San Francisco sometimes struggles to deal with mobile quarterbacks, as Patrick Mahomes also rushed for 49 yards against the Niners last season. Go with Murray 30+ rushing yards, at -110 odds.
- Cardinals vs 49ers Pick 1: Kyler Murray 30+ Rushing Yards @ -110 with bet365
Pearsall to Punch one in - Ricky Pearsall Anytime TD Scorer (+220)
Two games into the 2025 NFL season, 49ers wide receiver Ricky Pearsall ranks 11th in the league, with 164 receiving yards. Pearsall has been the biggest beneficiary of star wideout Brandon Aiyuk’s injury, and he will continue to be the 49ers top guy until Aiyuk returns.
Pearsall hasn’t yet caught a touchdown pass this season, but the Niners QBs are targeting him at a high rate. Mac Jones, filling in for Brock Purdy, threw the ball Pearsall’s way six times in last Sunday’s 26-21 win against the Saints.
Last season, Pearsall scored TDs in each of the 49ers last two regular season games, and he seems due for one soon. The odds on him to score a touchdown today against the Cardinals (+220) are certainly appealing.
- Cardinals vs 49ers Pick 2: Ricky Pearsall Anytime TD Scorer @ +220 with bet365
Cardinals to Catch the Niners Napping - Cardinals ML (+125)
Frankly, neither team has looked terribly impressive through the first two games. Sure, both the Cardinals and 49ers are 2-0, but they’ve played against teams that are projected to finish under .500 this season.
The 49ers are only slight home favorites for this one, and they will most likely be missing their QB, Brock Purdy. Mac Jones is a serviceable player, but he won’t necessarily be keeping the Cardinals coach, Jonathan Gannon, up at night.
Last season, Gannon’s Cardinals went 2-0 against the Niners. Kyler Murray is also 2-1 on the road against the Niners in his career. Arizona has every opportunity to steal this game and make a statement in the NFC West.
Take the Cardinals’ moneyline (+125) today.
- Cardinals vs 49ers Pick 3: Cardinals ML @ +125 with bet365
Cardinals vs 49ers Start Time
Kyler Murray and the Cardinals went 2-0 against the San Francisco 49ers in the 2024-25 season, but are underdogs today. Murray has had some of the best rushing games of his career against the Niners, who are missing key players like QB Brock Purdy and WR Brandon Aiyuk.
Cardinals vs 49ers Game Details
- Start Time: 4:25pm EDT
- Location: Levi’s Stadium
- Address: 4900 Marie P DeBartolo Way, Santa Clara, CA 95054
- TV & Streaming: Fox, Fubo, Sling