49ers vs. Panthers Odds, Spread, Preview: NFL Week 5 Predictions

49ers vs. Panthers Week 5 matchup preview and current betting lines

What could possibly happen when the NFL’s No. 1 defense (49ers) in many categories faces the No. 32 offense (Panthers) in yards and first downs? This is Baker Mayfield’s worst nightmare as he is already the lowest-rated quarterback in the NFL at ESPN with a 15.3 QBR this season. Now he draws a San Francisco defense that is allowing 11.5 points per game and hasn’t allowed a touchdown pass since Week 1.

Carolina’s punter is going to earn his paycheck. The 49ers are forcing a punt on 59.5% of drives and a three-and-out on 42.9% of drives this season, two incredible rates. The only thing that can screw this up is if Jimmy Garoppolo turns into a turnover machine on the road, which is not out of the realm of possibility.

Plus, Kyle Shanahan-coached teams tend to disappoint, especially when they are on the cusp of greatness or getting major props from a big win like Monday night against the Rams.

In his career as San Francisco’s head coach, Shanahan is 8-12-1 ATS as a favorite of at least six points. That’s not great, but a 15-6 SU record (.714) is also below average in that situation. Twenty-two teams since 2017 have a better wining percentage as a favorite of six-plus points than San Francisco.

The NFL Week 5 odds have the 49ers as a 6.5-point road favorite with a total of 39 points in this matchup. Do they deliver an easy win?

Players to watch in the 49ers vs. Panthers game

San Francisco 49ers

Brandon Aiyuk: Everyone knows about Deebo Samuel and George Kittle, but Aiyuk is an exciting receiver the 49ers don’t use enough. With Samuel getting carries out of the backfield and Kittle staying in more to block with left tackle Trent Williams out, Aiyuk could be a good prop bet for hitting his over in yards this week, if not scoring a touchdown. All 11 of his career receiving touchdowns are inside the 12-yard line.

Carolina Panthers

Brian Burns: He is the only Carolina defender with multiple sacks this season (3.0). When you play against Garoppolo, you need to get in his face as he will make a mistake that leads to a turnover. The Panthers are going to need at least two takeaways to win this game, and Burns is someone in the front seven who can help best with that.

49ers vs. Panthers prediction

Our Best NFL Bets for the 49ers vs. Panthers game

We have two NFL Week 5 predictions we want to share for this matchup of the best defense against one of the worst offenses.

49ers vs. Panthers Point Spread Pick: 49ers -6.5 (-110)

The 49ers vs. Panthers spread opened with the 49ers as 3-point road favorites, but it is quickly up to 6.5 as the Panthers look significantly outmatched on offense.

The nice thing about Carolina coach Matt Rhule is he will usually let you know after a quarter or two how his team’s game is going to turn out:

  • 0-16 in game-winning drive opportunities
  • 1-26 when allowing 17 or more points
  • 0-23 when allowing more than 21 points
  • 2-24 when not leading by at least 7 points at halftime
  • 3-26 when not leading by double digits at halftime

Carolina’s defense has four takeaways this season, but it has returned one for a touchdown in consecutive weeks. That is about the only way you could see this team covering in this matchup, if it intercepts a Garoppolo colorblind throw and returns it for a touchdown.

You can trust the San Francisco defense to deliver in this matchup. You just have to hope the offense doesn’t have a letdown and lets this one slip away. But I would take the 49ers to win by at least a touchdown.

Remember to check back with our NFL picks page for more betting tips.

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Total Points: Under 39 (-115)

Again, turnovers are the biggest fear in predicting this matchup. Not just for the return score potential but the short fields. That was what got Carolina’s game with Arizona over a mark like 39 points, because the game had a pick-six, and a Mayfield interception in the fourth quarter set Arizona up for a 5-yard touchdown drive. Then the Panthers turned it over on downs and the Cardinals had a 31-yard touchdown drive. In the blink of an eye, a 13-10 game in the fourth quarter was 26-10 and finished at 26-16.

But the fact is Carolina’s offense has scored 16, 15, and nine points in the last three weeks, and now they get a defense that has allowed one offensive touchdown drive in the last three games.

Not only are the 49ers crushing the pass, but they allow a league-low 2.9 yards per rush. So, it’s not even a good matchup for running back Christian McCaffrey, one of the few playmakers for the Panthers.

Even if it’s an ugly 20-10 or 20-13 game, that would more than satisfy the San Francisco cover and under we are envisioning for this matchup. Take the under 39 points for your NFL bet of the week.

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Frequently asked questions about the 49ers vs. Panthers game in week 5

The game is being played at Bank of America Stadium in Charlotte, North Carolina.

Coming into this season, Mayfield is 8-22 (.267) against teams with a winning record in his career. We won’t know for a few more months what San Francisco’s final record is, but the 49ers look like a winning team with this defense.

Be sure to keep up with our player prop picks and daily NFL predictions.