Panthers vs. 49ers Prediction & Opening Odds for Monday Night Football: NFL Week 12

Week 12 NFL action wraps up with the Carolina Panthers visiting the San Francisco 49ers on Monday Night Football. My best Panthers vs. 49ers prediction based on the opening odds expects a defensive slugfest at Levi's Stadium in Santa Clara, Calif. The 49ers are trading as a 6.5- or 7-point betting favorite ahead of kickoff at 8:15 p.m. ET (ESPN).

But instead of worrying about that line, I'm going to focus on the total as I continue my NFL Week 12 predictions.

🏈 Early Panthers vs. 49ers prediction & betting preview

Stay ahead with the rest of our early NFL picks for Week 12.

⬇️  Under 47.5 (-108) ⭐⭐⭐⭐

The Panthers have the second-most rushing attempts in the league, so it shouldn’t come as a surprise that three of their last five games have featured fewer than 30 points. Because of how much they run, they rank in the top 10 in the league in time of possession. However, they don’t do much with their long drives, ranking fifth-worst in points per game (18.8).

The 49ers rank 12th in rush defense and fifth-worst in pass defense. But the Panthers are a non-factor when it comes to throwing the ball, as they’re averaging just 187.2 yards per game. The 49ers have the second-ranked passing attack, but even if they score 30 for the third time in four games, the Panthers won’t score enough to push this Over.

DraftKings’ price of -108 implies a 51.92% chance that this Under hits. A $10 bet would profit $9.26.

Our Gary Pearson backs the Niners (-6.5) with his NFL picks against the spread, while Mike Spector suggests them in his NFL survivor pool picks.

📊 Live Panthers vs. 49ers odds: Week 12

See the latest NFL odds for every game in Week 12.

🔢 Panthers vs. 49ers opening odds

• Moneyline: Panthers +270 | 49ers -325
• Spread: Panthers +7 | 49ers -7
• Over/Under: Over 47.5 (-110) | Under 47.5 (-110)

↔️ Panthers vs. 49ers line movement

The overwhelming majority of bettors (75%) are backing the 49ers initially. With the 49ers’ last three wins coming by at least 10 points, and the Panthers scoring 16 or fewer in four of five, I expect bettors to continue to support the 49ers and this number to land at 7.5 or 8.

As for the total, three consecutive 49ers’ games have featured at least 58 points. With the Over hitting in more than half of each team’s games, I anticipate the Over getting some love, even if it’s not much. This will stay between 47 and 48 all week.

📈 Panthers vs. 49ers trends & betting notes: MNF

• The Over is 7-3-1 in 49ers’ games, and it has hit in three consecutive games
• The 49ers are 4-2 against the spread as a betting favorite
• The Over is 6-5 in Panthers games, but the total has only been set higher than 45.5 twice this season
• The Panthers are 2-1 against the spread as an underdog of 6.5 or more points

📺 How to watch Panthers vs. 49ers: Monday Night Football

• Date: Monday, Nov. 24
• Kickoff: 8:15 p.m. ET
• Location: Levi's Stadium (Santa Clara, Calif.)
• TV: ESPN