San Francisco 49ers vs. Arizona Cardinals Odds, Picks and Preview -- 10/10/2021

by Chuck Sommers

Game time: 4:25 p.m. ET, October 10, 2021
Venue: State Farm Stadium, Glendale, AZ
Where to watch: FOX

Opening Odds at USA Sportsbooks

DraftKings: Cardinals -5.5
BetMGM: Cardinals -5.5
Caesars: Cardinals -5.5

Season record
49ers: 2-2 (T-3rd, NFC West)
Cardinals: 4-0 (1st place, NFC West)

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49ers - Cardinals preview and analysis

Recent form
49ers: lost 28-21 vs. Seahawks in Week 4
Cardinals: won 37-20 at Rams in Week 4

For better or worse, the Trey Lance era could soon be upon us.

And what an opponent to usher it in. It’s only against the last undefeated team in the NFL with the likely MVP at the helm.

The San Francisco 49ers, minus starting quarterback Jimmy Garoppolo, will face Kyler Murray and the perfect Arizona Cardinals on Sunday in Glendale.

The Cardinals have proven that this start is no fluke. Arizona went into SoFI Stadium and pulled off the biggest jaw-dropping victory of this early season, holding the Los Angeles Rams to 20 points.

Arizona’s defense got an interception on Matthew Stafford and he still got his 280 yards. What was surprising about this win was the Cardinals didn’t sack Stafford once and yet shut down the passing game enough to keep it to 20 points.

What’s taking the NFL world by storm right now is the third-year quarterback and former No. 1 overall pick torching defenses with his arm and legs. Murray threw for 268 yards and two touchdowns while tacking on 39 yards on the ground. His 1,273 passing yards are third in the NFL and his nine passing touchdowns lead the league.

A.J. Green had his first big game since joining Arizona, catching five passes for 67 yards and a touchdown. DeAndre Hopkins also added 67 yards on four receptions, and Maxx Williams added the other touchdown with five receptions for 66 yards.

Chase Edmonds tacked on 120 yards on the ground, while James Conner ran for two touchdowns to pace the Arizona offense that tops the NFL with 35 points per game. The Cardinals defense is just as stingy, allowing 21.3 through four games.

The target is bigger on Arizona going forward, but to win in L.A. at that pace and not get a sack on Stafford is impressive. That’s the only gripe with this defensive line led by Chandler Jones and J.J. Watt, and they’ll want to right that wrong Sunday against, expectedly, the No. 3 overall pick in this year’s NFL Draft.

Garoppolo sustained a calf injury and will likely be out for a few weeks, barring any changes. Lance nearly engineered a comeback against a tough Seattle Seahawks defense, throwing for 157 yards and two touchdowns while also running for 41 in Levi’s Stadium in Santa Clara.

It wasn’t the most perfect game from Lance. He completed only 9 of 18 passes with a lot of throws looking off the mark and nearly intercepted. He nearly shortchanged the 76-yard touchdown to Deebo Samuel that got San Francisco going, but it has to bode well for his confidence that he nearly pulled it off.

Samuel had a team-best 156 yards on eight receptions and his first career two-touchdown game. George Kittle was held to 40 yards on four receptions and Trey Sermon led the way on the ground with 89 yards.


If it is Lance’s first start, this is going to end badly for him and head coach Kyle Shanahan. Arizona’s defense is chomping at the bits if that’s the case, and with Trent Williams’ status up in the air due to a knee injury, we could see the first big game for one Mr. Watt. San Francisco’s defense is going to be a hassle for Murray, but he’s already faced three good defenses and performed well. Cardinals by 14

Betting trends

The 49ers, who were favored by a field goal last week against Seattle, are 16-5 against the spread in their last 21 coming off an upset loss to a division rival.

San Francisco is 6-1 ATS in its last seven in games following a two-game homestand. The under is 6-0 in that stretch.

Arizona is 48-69 ATS as a home favorite since 1992, but 72-44 straight up. 

The Cardinals are 45-53 in their last 98 as a home favorite of seven points or less.

Players to watch

49ers: As noted earlier, George Kittle was held in check last week. He is looking for his seventh straight game of at least four receptions, however. Kittle had 92 yards in the last matchup last December. In order for that side of the ball to be efficient, Lance should look to Kittle for a lot of short, intermediate throws.

Cardinals: Chandler Jones hasn’t recorded a sack since the five-spot in Week 1 against the Tennessee Titans, but he has seven sacks in 10 career games against the 49ers.

Statistical leaders

Passing: Jimmy Garoppolo -- 925 yards, 5 TD, 2 INT
Rushing: Elijah Mitchell -- 146 yards, 1 TD
Receiving: Deebo Samuel -- 490 yards, 3 TD
Defense: Nick Bosa -- 4 sacks

Passing: Kyler Murray -- 1,273 yards, 9 TD, 4 INT
Rushing: Chase Edmonds -- 255 yards
Receiving: DeAndre Hopkins -- 225 yards, 3 TD
Defense: Byron Murphy -- 3 INT

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Chuck Sommers

About the Author:

Chuck Sommers has camped outside of sportsbooks since he can remember, learning the tricks and nuances of the trade. He still has nightmares of betting $5,000 on the Raiders in the Tuck Rule game but has since turned that to 25 years of veteran handicapping greatness. You can find him mostly in the shadows at the Red Rock or Aliante casinos wondering if the over is cashing on any given Sunday.

All photographic images used for editorial content have been licensed from the Associated Press.

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