San Francisco 49ers vs. Arizona Cardinals: Prediction, Odds, Depth Charts (12/17/23)

San Francisco 49ers vs. Arizona Cardinals kicks off Sunday (12/17/23) at 4:05 p.m. EST in Phoenix as a home game for the Cardinals. Get San Francisco 49ers vs. Arizona Cardinals predictions and best bets below. Our best bet is on the 49ers team total over 30.5 as their offense should continue to dominate.

San Francisco 49ers vs. Arizona Cardinals Prediction & Best Bet

Another week has come and gone, and the 49ers offense continues to dominate as the most efficient unit in football. At full health, the 49ers are near impossible to stop as they are loaded at the skill positions. Christian McCaffrey, Brandon Aiyuk, Deebo Samuel and George Kittle run wild in the open field while Brock Purdy hits them in stride under Kyle Shanahan’s unique schemes, posing as way too much offensive firepower for opposing defenses to try and stop.

When the offense is clicking, the 49ers are the best unit in football as their numbers suggest. As a whole, the 49ers offense ranks first in Off DVOA and EPA. They excel at both facets of the offense as well, checking in at first in Pass DVOA and third in Rush DVOA. A brunt of that success comes from their ability to routinely churn out yards at a time, ranking second in Rush Success Rate and first in Pass Success Rate. There is no weakness at the skill positions in the San Francisco armor when they have the ball in their hands.

The 49ers offense should have no issue continuing to hum against the Cardinals defense, one of the worst units in football. They rank 31st in Def Pass DVOA and 30th in Def Rush DVOA, all while generating one of the lowest rates of pressure to opposing backfields. This is in large part of their refusal to blitz, checking in at 29th in Blitz Rate. That spells disaster against Brock Purdy as he shreds opposing secondaries when in a clean pocket, grading out as the most efficient passer in the league per PFF.

It’s not enough for just the 49ers offense to put up points to cash this bet. The 49ers defense will need to get the Cardinals off the field early and often in order to give their own offense more opportunities to score. Kyler Murray is still showing signs of rust after another underwhelming passing performance, feeding into a 49ers coverage unit who ranks top-8 in Def Pass DVOA, EPA and Success Rate. The 49ers do struggle against the run yet may get the benefit of stacking the box until Murray can show he can constantly burn their secondary.

San Francisco 49ers vs. Arizona Cardinals Prediction & Best Bet: 49ers Team Total Over 30.5

San Francisco 49ers vs. Arizona Cardinals Betting Odds

This game has seen drastic changes in the spread since the lookahead line was set at -7, now climbing up to as high as -13.5 on the reopener. Bettors believe that was a slight overreaction, backing the Cardinals down to +13 in some shops. It’s tough to back that high of a number in a heavy variance sport, making this market a pass at this number.

As for the total, oddsmakers believed points would be scored at a moderate pace as they opened the number at 46. Bettors believe points will come at a faster rate by backing the over up to 48 as of writing. That is heavily predicated on the Cardinals ability to do their part, a feat that may be tough to come by with an underwhelming passing presence.

San Francisco 49ers vs. Arizona Cardinals Key Injuries

The Cardinals come into this one healthy while the 49ers defense currently has Arik Armstead, Dre Greenlaw and Charvarius Ward listed as questionable on their injury report.

San Francisco 49ers vs. Arizona Cardinals Key Matchups

Will Christian McCaffrey continue to run wild against the Cardinals front seven?

Christian McCaffrey vs. Arizona Cardinals Front Seven

Christian McCaffrey has been putting together an MVP type season, seriously rivaling Tyreek Hill for the Offensive Player of the Year award. While his touchdown streak has come to an end, that hasn’t stopped McCaffrey from putting up serious yardage.


He’s in a position to take advantage against a weak Cardinals defense who ranks 29th in Def Rush DVOA, 26th in Def Rush Success Rate, 23rd in Def Rush EPA, and 30th in Def Adjusted Line Yards. Factor in their tendency to anchor their linebackers and McCaffrey should find himself with plenty of open running lanes in the trenches for him to exploit.

San Francisco 49ers Depth Chart

QB: Brock Purdy
RB1: Christian McCaffrey
RB2: Elijah Mitchell
LWR: Brandon Aiyuk
RWR: Deebo Samuel
SWR: Jauan Jennings
TE1: George Kittle

Arizona Cardinals Depth Chart

QB: Kyler Murray
RB1: James Conner
RB2: Emari Demercado
LWR: Marquise Brown
RWR: Michael Wilson
SWR: Rondale Moore
TE1: Trey McBride

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Kody is a sports betting writer here at Lineups. He specializes in college sports as well as the NFL and NBA. He won’t quit believing in the Lions Super Bowl chances even when they are eliminated.

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