Skip to main content
Christian McCaffrey of the San Francisco 49ers runs with the ball as we share our favorite Cardinals vs. 49ers prediction.
Christian McCaffrey of the San Francisco 49ers runs with the ball against the New York Giants at Levi's Stadium on Sept. 21, 2023 in Santa Clara, California. Photo by Ezra Shaw/Getty Images via AFP.

We discuss if the Arizona Cardinals can cause an upset on Sunday in our Arizona Cardinals vs. San Francisco 49ers predictions based on the best NFL odds.

During the 49ers’ 30-12 Thursday Night Football win over the New York Giants in Week 3, running back Christian McCaffrey equaled Jerry Rice’s 36-year franchise record of scoring a touchdown in 12 consecutive games. McCaffrey is now just three away from tying the NFL record set by Washington’s John Riggins and former Buffalo Bills running back O.J. Simpson.

Although the Niners scored 38 points in both games against the Arizona Cardinals last season, they could face a challenge this Sunday, as Cardinals quarterback Joshua Dobbs has completed 72% of his passes in his first three matchups and has yet to throw an interception.

Here is our best Cardinals vs. 49ers prediction and NFL picks (odds via our best NFL betting sites; pick confidence based on a 1-to-5-star scale).

Cardinals vs. 49ers prediction

Christian McCaffrey Over 78.5 rushing yards (-114 via FanDuel) ⭐⭐⭐⭐

McCaffrey is averaging 118 rushing yards per game this season. Even with fellow rusher Elijah Mitchell taking carries from him against the Giants, CMC still ran for 85 yards. He is to Niners head coach Kyle Shanahan what back Terrell Davis was to Mike Shanahan’s Denver Broncos.

Only six teams have a worse rushing defense than Arizona. The Cardinals give up an average of 135 rushing YPG. They allowed 122 yards to Dallas Cowboys rusher Tony Pollard last week, and McCaffrey is set for a similarly big game.  

The 49ers have scored at least 30 points in six straight regular-season contests dating back to last season, the longest such streak in team history. Before that, the Rams ("The Greatest Show on Turf") were the last NFC team to score 30-plus points in at least six consecutive matchups,  from 1999 to 2000 (14 straight).

It’s no coincidence that San Francisco’s impressive run has included stellar performances from McCaffrey.

Not intended for use in MA
Affiliate Disclosure: Sportsbook Review may receive advertising commissions for visits to a sportsbook

Visit our Google News page and click "Follow" (⭐) for the latest odds, picks and news!  

Cardinals vs. 49ers best odds

FanDuel (-114)

McCaffrey Over 79.5 rushing yardsMcCaffrey Over 78.5 rushing yardsMcCaffrey Over 79.5 rushing yardsMcCaffrey Over 79.5 rushing yardsMcCaffrey Over 79.5 rushing yards

McCaffrey has averaged 99 rushing yards per game with the 49ers over his last eight regular season contests. The Niners’ explosive run game will be too strong for this Arizona defense.

The total has moved from 80.5 since Thursday. FanDuel gifts us an extra yard by setting its line at 78.5.

Cardinals vs. 49ers odds

Cardinals vs. 49ers odds analysis

The undefeated 49ers are heavy favorites to win Sunday. Our best sports betting apps have them priced as two-touchdown favorites. Arizona was a 12.5-point home underdog against the Cowboys last week and beat them 28-16. Head coach Jonathan Gannon’s Cardinals have covered in all of their games since he’s been in charge.

The points total is 43.5 points. Back the Over, with two of the NFL’s top three running backs taking the field.

There's no value in the Niners on the moneyline. Their odds are -900, so bet on the spread if you’re playing for a result.

Cardinals vs. 49ers game info

  • When: Sunday, Oct. 1 at 4:25 p.m. ET
  • Where: Levi’s Stadium, Santa Clara, CA
  • How to watch: Fox
  • Weather: 72 degrees, 0% chance of precipitation, 7-mph winds

Cardinals-49ers prediction made 9/29/23 at 3:54 p.m. ET

Kentucky bettors: Sports betting is here!

Kentucky sports betting launched on Sept. 28 - so sign up with the best Kentucky sportsbook promos now! And check out our list of the best Kentucky sports betting apps!

21+ and present in KY. Gambling Problem? Call 1-800-GAMBLER

NFL betting odds pages

Check out our best NFL betting sites:

(21+. Gambling Problem? Call 1-800-GAMBLER)
* Bonuses not applicable in Ontario.

Related pages