Last Updated Oct 08, 2021, 11:00 AM

San Francisco 49ers vs. Arizona Cardinals Predictions, Odds, Picks

Oct. 10, 2021
Joe Williams
VI Betting Expert

The San Francisco 49ers (2-2) hit the road Sunday to take on the NFL’s last unbeaten team, the Arizona Cardinals (4-0), at State Farm Stadium in Glendale, Ariz. Kickoff is scheduled for 4:25 p.m. ET, and the game will be televised on FOX.

Score Prediction: Arizona 31, San Francisco 20

Best Bet: Arizona -5.5

San Francisco 49ers vs. Arizona Cardinals Predictions

The 49ers head to the desert, but they’re going to have a much different look than the previous four weeks. That’s because rookie QB Trey Lance steps in under center for his first NFL start, as QB Jimmy Garoppolo exited last weekend’s game against the Seattle Seahawks due to a calf injury. That injury is expected to keep him sidelined for at least a game or two, if not more.

Meanwhile, the Cardinals blasted the Los Angeles Rams at SoFi Stadium, winning 37-20 in an NFC West showdown of unbeatens, covering a 3.5-point underdogs. Arizona’s offense has been producing on a week to week basis, showing no signs of slowing down.

San Francisco 49ers vs. Arizona Cardinals Betting Odds

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San Francisco 49ers vs. Arizona Cardinals Betting Resources

  • Matchup: NFC West
  • Date: Sunday, October 10, 2021
  • Venue: State Farm Stadium
  • Location: Glendale, Arizona
  • TV-Time: FOX - 4:25 p.m. ET

San Francisco 49ers Betting Analysis

Straight Up - SU, Against the Spread - ATS, Over-Under (O/U)

  • SU: 2-2
  • ATS: 1-3
  • O/U: 2-2
  • ATS - Home: 0-2
  • ATS - Away: 1-1

The 49ers were unable to withstand the loss of Jimmy G, although Lance did show some glimpse of brilliance in his first extended action as a pro. It was the second straight loss for San Francisco, and it fell to 1-3 ATS overall. The Niners have alternated OVER and UNDER results in each of their four outings, too.

It’s the first time back on the road since opening the season in Detroit in Week 1, and Philadelphia in Week 2. The 49ers stayed on the road and practiced between games in West Virginia at Greenbrier. Those two teams are a combined 1-7 SU, too. This will be a much, much more stern test, as they try and slow the Cardinals down.

I think the 49ers are going to struggle mightily with Lance under center, and he’ll be coaxed into making a handful of miscues.

Arizona Cardinals Betting Analysis

Straight Up - SU, Against the Spread - ATS, Over-Under (O/U)

  • SU: 4-0
  • ATS: 3-1
  • O/U: 2-2
  • ATS - Home: 0-1
  • ATS - Away: 3-0

The Cardinals look to keep their record unblemished, and keep the 1972 Miami Dolphins from celebrating. Arizona’s offense has kept on ticking, going for 31 or more points in each of its four games to date. It’s hard to believe the Jacksonville Jaguars defense actually allowed the fewest amount of points to the Cards.

Not only are the Cardinals winning, but they’re cashing tickets for bettors who back them, too. They have covered back-to-back games, and three of four overall. Of course, the non-cover for Arizona was its only home game to date, a 34-33 nail-biter against the Minnesota Vikings.

Arizona leads the NFL with 440.5 total yards per game and 35.0 PPG. They’re also third in the league with 304.0 passing yards per contest, and 136.5 rushing yards per outing to rank sixth. Defensively, Arizona has been just good enough, ranking 15th in total yards allowed. They’re ninth in the NFL with 21.3 PPG allowed. If they struggle in any one area, it’s against the run, allowing 135.8 yards per game. However, San Francisco is a bit banged up in the run department, and that’s a non-issue here.

Inside the Stats - San Francisco 49ers

  • Record: 2-2
  • Division Standing: 3rd - NFC West
  • Points Scored: 107
  • Points Allowed: 102
  • PS/G: 26.8 (7th)
  • PA/G: 25.5 (22nd)

Inside the Stats - Arizona Cardinals

  • Record: 4-0
  • Division Standing: 1st - NFC West
  • Points Scored: 140
  • Points Allowed: 85
  • PS/G: 35 (1st)
  • PA/G: 21.3 (9th)

Key Players to Watch

  • SFO: Trey Lance - QB (10/19, 162 yards, 3 TD)
  • SFO: Deebo Samuel - WR (28 catches, 490 yards, 3 TD)
  • ARI: Kyler Murray - QB (102/134, 1,273 yards, 9 TD, 4 INT)
  • ARI: DeAndre Hopkins - WR (17 catches, 225 yards, 3 TD)

San Francisco 49ers vs. Arizona Cardinals Betting Conclusion

Regardless of the quarterback situation, I’d like the Cardinals on their home field. But with the rookie Lance under center, I think the Arizona defense is able to confuse him early and often. Toss in the fact that TE George Kittle is expected to play, but he is a little bit banged up, I think the 49ers have a tough time keeping the Cardinals within their sights.

Arizona has just shown no signs of letting up, and you had to figure they might struggle against the Los Angeles Rams in a road game last week. Instead, they ended up burying the Rams in the marquee game. Look for the home side to do the same against the 49ers. Arizona is 5-1-1 ATS in the past seven meetings in this series, and the Cardinals will improve upon that mark here.

San Francisco 49ers vs. Arizona Cardinals Betting Trends

  • San Francisco has seen the underdog cover the spread in nine of its last 10 games.
  • Arizona has won four straight games.
  • Arizona has gone OVER the point total in six of its last seven home games.

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