49ers vs Panthers Week 5 Picks and Predictions: Carolina Hunted at Home

The San Francisco 49ers don’t have long to celebrate their convincing win over the rival Rams on Monday, with a quick turnaround to visit the Carolina Panthers in Week 5.

San Francisco improved to 2-2 straight up (2-2 ATS) with a 24-9 victory at home in primetime, showcasing a nasty pass rush that picked up seven sacks in the win over L.A. Now, the Niners run into an awful offensive line in Carolina and a quarterback in Baker Mayfield who’s a mess when under pressure. 

This spread currently sits below the key number of a touchdown, with San Francisco set as 6.5-point road chalk. I run down the tale of the tape for point spread and Over/Under total as well as give my best NFL picks and predictions for 49ers vs. Panthers on Sunday, October 9.

49ers vs Panthers best odds

49ers vs Panthers picks and predictions

Regardless of the short week and home-field edge for Carolina, there are more than 6.5 points separating these teams right now.

The Panthers are stuck with Baker Mayfield at quarterback for the immediate future and have said as much. Backup Sam Darnold and rookie QB Matt Corral are on the IR, leaving defacto fourth-stringer P.J. Walker as the only other option under center.

Mayfield has been awful and faces a Niners defense that seems tailor-made to terrorize him. San Francisco is coming off a seven-sack performance on Monday Night Football, has 15 sacks in total on the year, and owns the highest pressure rate per dropback in the NFL (34.2%) despite blitzing only 22.4% of the time.

That means the Niners are destroying offensive lines with the front four while dropping linebackers in coverage or putting an LB spy on the running back. That’s helped the 49ers rank No. 1 in Run Defense DVOA at Football Outsiders and gives them a decisive edge against the Panthers’ top weapon: RB Christian McCaffrey.

Carolina’s offensive line hasn’t provided much pushback against pass rushes through four weeks, sitting 28th in adjusted sacks. If McCaffrey can’t get loose against the San Francisco run stop and the Panthers trail early on, Mayfield could be dropping back more than the team would like. He’s wretched under pressure, completing only 48% of passes in those situations.

As for the 49ers' offensive attack, Kyle Shanahan’s methodical and physical offense will wear down a Panthers defense that has played the most of any stop unit in the NFL this season. San Francisco is plodding with a play every 30.06 seconds (fifth-slowest) and keeps you guessing with pre-snap movement and a balanced playbook, running the ball on 51.68% of snaps. 

The Panthers’ defense has buckled in the second half of games, after getting little respite or support from a listless offense. Carolina owns the No. 3 first-half Defensive DVOA but sees that metric balloon to 31st in the final two quarters. The team has allowed 85 total points on the year, with 59 of those coming in the second half (69%).

It could take a little while, but the Niners will eventually break the Panthers on both sides of the ball and cover this 6.5-point spread in Week 5.

My best bet: San Francisco -6.5 (-110)

49ers vs Panthers spread analysis

The look-ahead line for this game set back in the summer had San Francisco as a 4-point road favorite, with optimism around the Panthers’ acquisition of Mayfield. That shine has definitely come off that trade since the start of the schedule.

Carolina is just 1-3 SU and against the spread heading into Week 5, with a Mayfield-led offense ranked dead last in EPA per play. And while San Francisco’s scoring attack has taken a step back with Jimmy Garoppolo under center, the Niners’ defense remains elite. 

San Francisco is No.1 in Defensive DVOA at Football Outsiders — including the top-ranked run stop in that advanced metric. That doesn’t bode well for a Panthers playbook leaning heavily on McCaffrey to pick up gains on the ground.

Before the 49ers’ impressive outing on Monday, the early line available was as low as San Francisco -4.5. However, Tuesday morning, that official opener hit the board at Niners -6 and promptly jumped as high as -6.5 across the industry. A short week and some injured starters for the 49ers defense are keeping this spread below a touchdown as of Thursday afternoon.

According to PointsBet books, 85% of bets and 84% of handle is backing San Francisco on the road. Our Covers Consensus confirms that sentiment, with 68% of picks on the visitor. 

49ers vs Panthers Over/Under analysis

This total had a look-ahead number of 43 points back in the summer, as both teams were projected to have above-average stop units in 2022. And for the most part, those projections are correct.

San Francisco sits among the elite defensive groups in many advanced metrics and is also tops in points per play allowed (0.187) and yards per play (3.8) entering Week 5. Carolina’s stop unit is ninth in yards allowed per play (5.0) and 12th in points per play allowed (0.306) as well as a respectable 12th in Defensive DVOA at Football Outsiders, despite playing more minutes than any other stop unit in the league (35:42 TOP allowed).

This opening total was set at 39.5 points and has slimmed half a point to 39 at most shops as of Thursday. The 49ers boast a perfect 0-4 Over/Under count while the Panthers sit 1-3 O/U after four weeks of football betting.

PointsBet books are reporting interesting splits, with 60% of total bets on the Over but 69% of money taking the Under.

49ers vs Panthers betting trend to know

Carolina head coach Matt Rhule is a gag-inducing 5-14 SU and ATS at home since joining the Panthers in 2020, including a 1-2 SU and ATS mark in 2022. Find more NFL betting trends for 49ers vs. Panthers.

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