49ers vs Cardinals Week 3: Expert Prop Bets, Spread Pick

The Arizona Cardinals and San Francisco 49ers are set for a Week 3 clash at Levi's Stadium.

While fans on both sides will be watching, plenty of other attention will be had thanks to fantasy and betting.

Three of the best prop bets we could find on the internet, plus a spread pick:

Deebo Samuel ANYTIME TD Scorer

San Francisco 49ers WR Deebo Samuel — Aug 6, 2026; Santa Clara, CA, USA; San Francisco 49ers wide receiver Deebo Samuel Sr. (19) during training camp at SAP Performance Facility. Mandatory Credit: Sergio Estrada-Imagn Images | IMAGN IMAGES via Reuters Connect

Josh Inglis, Covers.com: "Deebo Samuel led the team in route share in a similar spot last week as a huge favorite. The 49ers still had a 4.4% PROE (eighth best) despite the positive game script, which keeps me hopeful that Brock Purdy will keep slinging it. The overall play volume wasn't huge, but Samuel tied for the team lead in targets and had a rush, which was his second in two weeks.

"Samuel could have a path to more targets in Week 3 with Demarcus Robinson out and Mike Evans becoming more questionable after being a DNP at practice Wednesday. Purdy is playing at an MVP level, and Samuel has a role around the goal line, as he is tied for the team lead in RZ targets with three and has one score."

Jacoby Brissett UNDER 226.5 Passing yards

Jacoby Brissett, Arizona Cardinals — Arizona Cardinals quarterback Jacoby Brissett (7) throws a pass against the Seattle Seahawks during a game at State Farm Stadium in Glendale, Ariz. on Sept. 20, 2026. | USA TODAY Network via Reuters Connect

Iain MacMillan, SI.com: "Jacoby Brissett is averaging just 186.0 passing yards per game through the first two weeks, and now he has to face a revamped 49ers defense that has done a stellar job of stopping the pass through the first two weeks. The 49ers have given up just 175 passing yards per game, while ranking third in opponent dropback success rate.

"I'm surprised to see Brissett's passing yards total being as high as it is. I'll bet the UNDER."

Christian McCaffrey OVER 13.5 Rushing Attempts

San Francisco 49ers RB Christian McCaffrey — Aug 3, 2026; San Francisco, CA, USA; San Francisco 49ers running back Christian McCaffrey (23) during training camp at Levi's Stadium. Mandatory Credit: Sergio Estrada-Imagn Images | IMAGN IMAGES via Reuters Connect

Derek Carty, Action Network: "THE BLITZ is forecasting 17.48 rush attempts for Christian McCaffrey. The oddsmakers' implied projection is 14.26 rush attempts, so I believe there is some value here. If you take the over, you’d be projected to win 67% of the time resulting in a 33% ROI with expected value of $33.12 (based on a $100 wager)."

Spread: Cardinals +8.5

Arizona Cardinals HC Mike LaFleur — Arizona Cardinals head coach Mike LaFleur interacts with his players before their game against the Seattle Seahawks at State Farm Stadium in Glendale on Sept. 20, 2026. | USA TODAY Network via Reuters Connect

FanDuel Staff: "The 49ers have certainly been fantastic thus far, sitting at 2-0 while averaging 31.0 points per game, and their offense has produced 6.7 yards per play. Arizona hasn't been nearly as efficient on O, averaging 16.5 points and just 4.6 yards per play, so this certainly isn't a bet based on the Cardinals having the better underlying profile.

"Instead, the appeal is the number and San Francisco's growing injury issues. Wide receiver Demarcus Robinson is expected to miss multiple weeks with a high-ankle sprain, while Mike Evans exited last week's game with a hip injury and may be less than 100% even if he suits up. The 49ers were already dealing with several injuries elsewhere — including some to other pass-catchers — potentially leaving them thinner than their 2-0 record suggests."

Odds refresh periodically and are subject to change.

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