49ers vs. Cardinals NFL Week 5 Picks and Expert Insights

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Defensive-line J.J. Watt #99 of the Arizona Cardinals. Christian Petersen/Getty Images/AFP

Back in August, long before most would have thought about this encounter, those top sportsbooks that released early point spreads had San Francisco favored. Since then, things have changed dramatically.

YouWager and other top sportsbooks have established Arizona as 5.5-point home favorites. If that sounds like a lot of points against San Francisco, let’s delve into both teams to understand why.

San Francisco 49ers vs. Arizona Cardinals

Sunday, October 10, 2021 – 04:25 PM EDT at State Farm Stadium

While most sharp betting experts don’t have Arizona at the top of their power rankings this week, rest assured, they have moved up quickly since the season started. The Cardinals are the NFL’s lone undefeated club and they have the national media, handicappers, and sports bettors taking a good look at them this week trying to understand why.

Just How Good Is San Francisco?

After last year’s post-Super Bowl depression and injury-plagued season, the feeling was the Niners were mostly intact from that season and would be an NFC West division contender again. Things started well with a 2-0 start, both victories coming on the road.

After a languid first half against Green Bay at home, the 49ers stormed back to take the lead, but they couldn’t contain Aaron Rodgers in the final minute to lose. Last week against Seattle, they dominated the Seahawks in the first two quarters, yet were only tied. Russell Wilson got hot, Jimmy Garoppolo suffered a calf injury and rookie Trey Lance could not establish offensive continuity and they faltered again.

Garoppolo’s injury is not as bad as first feared but he’s still questionable. Though San Fran is well down the depth chart at running back, that’s the first key to their success this week, with the Cardinals 26th against the run and 31st in yards per carry allowed.

The 49ers are still a good club, they just need a sustained effort for all four quarters.

Arizona’s Personnel Is Better Than Believed

Coach Kliff Kingbury wanted Kyler Murray when he took the job in the desert. He got him. In the last two years, the offensive line was quietly upgraded and wide receivers, DeAndre Hopkins and A.J. Green were added. Both players were somewhat assumed to be on the downside of their careers, but both are reenergized among the many cactuses.

On defense, the addition of J.J. Watt has freed up Chandler Jones and Cards' defense is more aggressive. Another massive factor is the secondary. Budda Baker is a do-everything safety and the emergence of cornerbacks Byron Murphy Jr. and Robert Alford, who are stickier than Gorilla Glue, have made this unit a top-flight secondary.

However, Murray is the catalyst and at this time he’s playing as well as any QB in the league. His passes are on target, he’s seeing the entire field with great vision and he’s almost unstoppable when he takes off running. Murray is leading the NFL’s No. 1 offense in scoring and yard gained and he’s got more ways to escape than MacGyver. This is a treacherous club.  

And the Winner Is…

It seems there is a simple explanation for the betting odds. San Francisco is -6 in turnover margin and Arizona is +5. Good enough right, especially if Lance has to start his first game on the road or Jimmy G is in some way compromised.

Yet, as we have said many times, this is the National Football League and when making NFL picks, you have to think differently and use all available information. For instance, the 49ers are 16-5 ATS off an upset loss to a division rival as a favorite. Some might forget the Redbirds were incredibly lucky to beat Minnesota 34-33 in Week 2 on a short missed field goal at the buzzer as 3.5-point home favorites. Going back to 2019, with the spread setback, the Cards are 1-8 ATS as home faves.

Arizona might win, they just don’t beat the number.

NFL Pick: 49ers +5.5 (-110) at YouWager (visit our YouWager Review)

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49ers +5.5 (-110)
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*The line and/or odds on picks in this article might have moved since the content was commissioned. For updated line movements, visit BMR’s free betting odds product.