Cardinals vs. 49ers Odds & Picks: Are Kyler & Co. the Smart Play?

Cardinals at 49ers Betting Odds

• Odds: 49ers -10
• Over/Under: 45
• Kickoff: 4:05 p.m. ET
• TV Channel: FOX

Odds as of Thursday evening and via PointsBet, where Action Network users can access an exclusive promotion to get a 200% deposit match (deposit $50, bet with $150).No strings attached. No rollover required.

The San Francisco 49ers were the last of the undefeated teams to fall this season, but they'll have a chance to bounce back against the division rival Arizona Cardinals this Sunday.

The 49ers are one of three teams favored by double digits in Week 11, but bettors are siding heavily with the Cardinals to cover with 79% of tickets backing them (see live public betting data here).

Can Kyler Murray and Co. stay within the number on the road?

Our experts break down every angle of this matchup, featuring Sean Koerner’s projected odds and staff picks.

Cardinals-49ers Injury Report

Which team is healthier? Cardinals

The Cardinals put out a lengthy injury report, but David Johnson wasn't on it, though Chase Edmonds (hamstring) was. It looks like Arizona will be rolling with DJ and Kenyan Drake in the backfield while Edmonds nurses his hamstring.

The 49ers are a disaster on the injury front given Matt Breida (ankle), George Kittle (knee) and Emmanuel Sanders (ribs) all haven't practiced this week. It sounds like Breida and Kittle are expected to be out, but the 49ers are still holding out hope that Sanders can suit up. — Justin Bailey

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

Biggest Mismatch

Cardinals Rush Offense vs. 49ers Rush Defense

The Cardinals almost upset the 49ers two weeks ago, losing 28-25 at home.

While the Niners have the second-best defense in the league, they've been vulnerable against the run. In their 27-24 loss to Seattle, they allowed 147 yards at 4.3 yards per carry.

More importantly, the Cardinals gashed the 49ers in their first meeting for a total of 153 rushing yards and an average of 6.7 yards per carry. The newly-acquired Drake rushed for 110 yards at 7.3 yards per carry.

Besides Drake, the Cardinals will also benefit from the return of Johnson, who has four weeks of RB10 performances or better.

The 49ers rank first among all teams in pass defense efficiency (yes, even ahead of the Patriots). The loss of linebacker Kwon Alexander to a torn pectoral muscle is also a huge absence for the 49ers.

Murray totaled 324 passing yards and three touchdowns last week at Tampa Bay. The Cardinals' spread offense creates wide running lanes for their versatile backs.

The Niners will need to greatly improve against a Cardinals running game that found season-best success in their first matchup. — Mike Randle

Sean Koerner's Projected Odds

• Projected Spread: 49ers -12
• Projected Total: 45.5

These two teams met just two weeks ago. The 49ers managed to pull off the win in what turned out to be a 28-25 nail-bitter, then followed that up with their first defeat of 2019. But I expect the Niners to bounce back this week.

The public appears to be backing the Cardinals with the majority of tickets coming in on Arizona. We’ll need to see if Sanders and/or Kittle are able to suit up. If they’re both active, I’d set the 49ers at -12.5, but if they’re both ruled out, I’d set it at -11.5. — Sean Koerner

PRO System Match

Since 2003, the under is 820-726-29 (53.0%) in division games. Unders have been a smart play in division games as increased familiarity between teams creates a lower-scoring environment.

It may seem obvious to some bettors, but it has been more profitable to take the under in division games with high totals (more than 44 points). It is just easier for unders to cash when more points are expected to be scored.

Following this Pro System, bettors have gone 180-109-3 (62.0%) since 2003. A $100 bettor would have returned a profit of $6,206 following this strategy.

A slight majority of bets are on this over, but history suggests the under is a smart play. — 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

John Ewing: Cardinals +10

San Francisco suffered its first loss in Week 10, but oddsmakers expect the 49ers to bounce back against the Cardinals, having initially opened Kyle Shanahan's team as 14-point favorites.

On the surface this matchup favors the 8-1 Niners, but there are a few reasons to think this line is inflated. For starters, it's historically been profitable to fade teams that have been easily covering the spread.

The 49ers have covered the spread on average by more than five points per game, making them a match for this system that has gone 389-312-21 (56%) against the spread since 2003.

Then there's the Niners defense, which is second in Football Outsiders' DVOA but has been susceptible to the run — San Francisco has allowed 4.6 yards per carry (24th). This matchup sets up well for a Cardinals team that's averaged 4.9 yards per attempt this season.

Our simulations project the 49ers to win on average by nine points. Sharp bettors agree as they've bet this line down to San Francisco -12. Even though the line has moved, there is still value on the Cardinals. I would bet Arizona down +10.

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