Cardinals vs 49ers Week 18 Picks and Predictions: Lifeless Cards Handed One Last Embarrassment

Arizona's season was a nightmare even before Kyler Murray tore his ACL and it's only gotten worse. The good news: It's Week 18. The bad news: The 49ers are going to hand the Cardinals one final smackdown, as our NFL picks explain.

Daniel Dobish
Last Updated: Jan 8, 2023 8:28 AM ET Read Time: 4 min
Fred Warner San Francisco 49ers NFL
Photo By - USA TODAY Sports

The Arizona Cardinals and San Francisco face each other in Week 18 in the regular season finale Sunday at Levi’s Stadium in Santa Clara.

The Cardinals have been long eliminated from the chase for an NFC playoff spot, while the 49ers are still in the mix for the No. 1 overall seed in the conference and the home-field advantage which comes with it.

The 49ers picked up a scintillating 37-34 overtime in Las Vegas last weekend to win for the ninth consecutive time. The non-cover did snap a 6-0 ATS run for San Fran, though.

Can the Cardinals rise up and hand the 49ers a costly loss, derailing their mine cart from reaching NFC gold? Or will the 49ers secure the bag, and perhaps earn a first-round bye? 

We’ll discuss in our NFL picks and predictions for Cardinals vs. 49ers on Sunday, January 8.

Cardinals vs 49ers best odds

Cardinals vs 49ers picks and predictions

The big news out of this week’s game for the Cardinals is that future Hall of Famer J.J. Watt will be playing his final regular-season game. The 33-year-old has still looked like he is in his prime, posting 10.5 sacks this season, including five in the past five games.

The starting quarterback for Watt’s final game is… David Blough. The former Purdue starter, who had a brief cup of coffee with the Lions, makes his second straight start to close out the season.

Toss in the fact Blough will not have James Conner in the backfield, while Robbie Anderson is also out, and this team has some issues on offense. 

On defense, outstanding rookie Marco Wilson has a questionable tag due to a neck injury, and Josh Jackson and Leki Fotu also carry the same designation. Zach Allen and CB Antonio Hamilton are out, too, making matters worse for the beleaguered Cards.

The 49ers are in much better shape, although spark-plug Dre Greenlaw is out, and Javon Kinlaw is questionable. The team received great news when Brock Purdy, Christian McCaffrey, and, perhaps most importantly, Deebo Samuel, each practiced in full Friday, and no longer carry an injury designation.

The 49ers are hungry for a championship, while the Cardinals are starting a fourth-string signal caller while missing its top back and some key defenders. This has the potential to be really ugly, and it’s rather shocking the line isn’t much higher. Take advantage.

My best bet: 49ers -14 (-110 at BetMGM)

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Cardinals vs 49ers spread analysis

Credit the Cardinals for covering last week in a 20-19 loss in Atlanta against another fellow non-playoff team. The Falcons won on a field goal at the buzzer, but the Cards played hard, Blough threw for 222 yards and a score, and Conner ran well for three quarters before getting hurt.

Again, Conner is out this week, and that means Corey Clement and Keaontay Ingram will handle the workload, but that’s a tough ask against a Niners rush defense that is tops in the league, allowing just 78.8 yards per game on the ground.

In fact, San Francisco’s defense, as a whole, led by defensive coordinator DeMeco Ryans, is a great group. The 49ers allow a league-best 16.5 PPG, and just 303.4 total yards per contest, which is second overall. 

A bevy of backups and journeymen aren’t going to be able to unlock the Rubik’s Cube that is San Francisco’s D, if much better caliber players before them have been unable to do so.

San Francisco pounded Arizona 38-10 in the first meeting on November 21 in the first meeting, touching out a six-game cover streak for the Niners. You can expect a similar result here, if not an even more lopsided score.

Cardinals vs 49ers Over/Under analysis

All of the talk about San Francisco usually falls upon its defense, and rightly so, and I did the same above. But the offense is pretty good, and all of its key contributors will be on the field.

As mentioned, Purdy, CMC, and Deebo are healthy and off the injury report, while Brandon Aiyuk has been a force, and George Kittle is once again a game changer, finally back to 100 percent while playing like a superstar again.

This game has a total below 40 or 39.5 at most shops. The first inclination might be to slam the Under, and nearly 90 percent of the money is going in that direction.

However, think for a second. San Francisco dropped 38 on Arizona in the first meeting, when the Cardinals were still relatively healthy and had something still to play for. The 49ers will now be doing everything in their power to not only win but to do so in emphatic fashion, trying to leave no doubt while playing at the same time as the Cowboys and Eagles, two teams also vying for the No. 1 overall seed in the NFC.

I can see the 49ers taking care of the Over all on their own here, needing little to no help from the Cardinals to inch across the finish line. Over and 49ers is a nice, late holiday gift parlay.

Cardinals vs 49ers betting trend to know

The Cardinals are 1-7 ATS in the past eight games against the NFC West, while going 1-4 ATS in the past five games against winning teams. Find more NFL betting trends for Cardinals vs. 49ers.

Cardinals vs 49ers game info

Location: Levi's Stadium, San Francisco, CA
Date: Sunday, January 8, 2023
Kickoff: 4:25 p.m. ET
Opening odds: 49ers -13.5, 40.5

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