49ers vs. Cardinals Betting Odds & Preview: Can You Trust SF As A Large Favorite?

49ers at Cardinals Betting Odds & Picks

• Odds: 49ers -10
• Over/Under: 42.5
• Kickoff: 8:20 p.m. ET
• TV Channel: FOX, NFL Network, Amazon Prime

Odds as of Wednesday evening and via PointsBet, where Action Network users can access an exclusive promotion to get a 200% deposit match (deposit $50, bet with $150).

The San Francisco 49ers are still undefeated at 7-0 and are 5-2 against the spread on the season, so it's no wonder why bettors are buying them, moving them from 7- to 10-point favorites. But is this spread for this Thursday Night Football showdown against the Arizona Cardinals now inflated?

Our experts break down the betting odds and market, complete with staff picks.

Thursday Night Football Injury Report

Which team is healthier? 49ers

The Cardinals have ruled out Chase Edmonds (hamstring) and listed David Johnson (ankle) as questionable, though DJ did practice on Wednesday. Still, neither is surprising after Arizona traded for Kenyan Drake earlier in the week. OL Justin Murray (knee) is also questionable, and a short handed offensive line against the 49ers wouldn't be ideal.

The 49ers are trying to remain optimistic about Matt Breida (ankle), but is questionable after getting in two limited practices. Raheem Mostert (knee) was also downgraded, leaving Jeff Wilson and Tevin Coleman as the healthy running backs. — Justin Bailey

Note: Info as of Wednesday. See our Injury Report for daily practice participation and game statuses up until kickoff.

Biggest Mismatch

49ers Rushing Attack vs. Cardinals Rush Defense

The 49ers have pounded the ball down the throat of every opponent they've faced this season. They're averaging 181.1 rushing yards per game, second only to Baltimore. They eviscerated the Carolina run defense last week, totaling 232 rushing yards and 6.1 yards per carry while scoring five rushing touchdowns.

San Francisco (7-0) is one of two undefeated teams left and is a perfect 4-0 on the road heading into Arizona to face a Cardinals defense that ranks 26th in Football Outsiders' run defense DVOA.

Since their Week 1 tie with Detroit, the Cardinals have allowed more than four yards per carry to every opponent, including more than five yards per carry to Baltimore and Carolina.

Arizona is also by far the NFL's worst team at limiting opposing tight ends, allowing more than 17 points per game to the position. That’s bad news against top-three overall tight end George Kittle, especially with Emmanuel Sanders complicating the defensive focus even more.

The Cardinals' best plan of attack is to limit the 49ers rushing game and hope to force game-manager quarterback Jimmy Garoppolo into mistakes. But considering we have yet to see any team even marginally limit the San Francisco running attack, it's highly unlikely the low-efficiency Arizona defense will have much luck. — Mike Randle

PRO System Match

The 49ers have moved from 7- to 10-point favorites since opening. They're undefeated while the Cardinals were blown out in Week 8, so it's easy to understand why the line is moving.

More than 80% of spread tickets are on the Niners to cover as of writing (see live public betting data here), but it's important to not overreact to one game. The Cardinals didn't play well in their 31-9 loss to the Saints, but teams are never as good or as bad as they looked the week prior.

Historically, it's been profitable to bet teams getting little public support after a bad offensive game. Bettors following this Pro System have gone 150-95-4 (61.2%) against the spread since 2003, returning a profit of $4,606 for a $100 bettor.

Casual bettors are expecting another win and cover for the 49ers but don’t be surprised if the Cardinals keep this game close. — John Ewing

PRO Systems are data-driven betting strategies that turn winning long-term trends into easy-to-follow picks, all handpicked and monitored by our team of analysts. Try Action PRO now and instantly access real-time game matches for every PRO System.

Expert Picks

PJ Walsh: Cardinals +10

As Ewing mentioned above, Arizona is a match for our Bet Against Public After Bad Game Pro System, which has produced a stellar 61.2% against-the-spread (ATS) win rate since 2003.

But this isn’t the only historically profitable betting angle pointing toward the Cardinals — our Fade Covering Teams Pro System also suggests that San Francisco is overvalued in this matchup.

It's not surprising to see bettors blindly backing teams that have won them money in recent weeks, but oddsmakers don't blindly set lines. They know this one-sided action is coming ahead of time, and will set lines that force bettors to take shaded numbers when playing the popular side of a matchup like this one.

Therefore, contrarian-minded bettors can scoop up extra line value by making the ugly play with the underdogs, which in this case is the Cardinals. [In New Jersey? Bet now at PointsBet]