NFL Week 16 Best Bets (Predictions for Buccaneers vs. Panthers, Bills vs. Browns on Sunday)

The SI Betting team breaks down their favorite bets for Week 16 of the 2025 NFL season, including a pick for Buccaneers vs. Panthers matchup.

The Carolina Panthers and quarterback Bryce Young are underdogs in Week 16. / Scott Kinser-Imagn Images

There are just 19 teams still alive to make the playoffs (two have clinched) entering Week 16, and a ton of massive games are set to take place on Sunday.

So, why don't we place a few bets?

Each week, SI’s Peter Dewey and Iain MacMillan share their favorite bets for Sunday’s games every week, and we're coming a strong Week 15, where we cashed both of our picks.

Dewey took an underdog in the Denver Broncos, who ended up winning outright to stay undefeated at home in a marquee matchup against the Green Bay Packers. In addition to that, MacMillan cashed a pick for the Los Angeles Rams as 5.5-point favorites against the Detroit Lions. L.A. made a major comeback to remain in the No. 1 spot in the NFC through 15 weeks.

You can't complain about a perfect week, and we're looking to build on that in Week 16 with a ton of great games on Sunday's slate. There are a pair of Saturday games too, but for the sake of this column we're only focusing on Sunday's action.

This week, we're eyeing a pair of home underdogs, including a bet for the NFC South battle between the Tampa Bay Buccaneers and Carolina Panthers.

Here's a breakdown for each of these picks, and their latest odds, for Week 16!

NFL Best Bets for Week 16

Odds via DraftKings Sportsbook and FanDuel Sportsbook.

• Carolina Panthers +3 (-112) vs. Tampa Bay Buccaneers – Peter Dewey
• Cleveland Browns +10.5 (-122) vs. Buffalo Bills – Iain MacMillan

Carolina Panthers +3 (-112) vs. Tampa Bay Buccaneers – Peter Dewey

The NFC South is on the line over the next three weeks, and I’m buying the Carolina Panthers and Bryce Young as home underdogs on Sunday against the Tampa Bay Buccaneers. 

Tampa Bay has really struggled as of late, going 2-6 over its last 10 games, and it’s lost back-to-back games as a favorite against New Orleans and Atlanta. While the Panthers lost to New Orleans as a favorite in Week 15, it has been much better when set as an underdog in 2025: 

• Carolina is 4-2 against the spread at home.
• The Panthers are 7-4 against the spread as underdogs.
• Tampa Bay is just 2-5 against the spread as a favorite.

I wouldn’t be shocked if Carolina keeps this game within a possession, and the Bucs’ offense has been extremely concerning as of late. Tampa Bay has slipped behind the Panthers in EPA/Play on offense (now 24th), and the Bucs are also just 18th in the league in EPA/Play on defense. 

The Buccaneers are going to need to lean more on their run game (seventh in EPA/Rush), as they’ve struggled throwing the ball (24th in EPA/PAss) since the halfway mark of the season. 

The Panthers also outrank Tampa Bay in yards per play defensively, so I don’t think there’s a huge difference between these teams. 

I’d much rather take the Panthers as home dogs, especially since this spread has moved from 1.5 to 3 over the course of the week.

Cleveland Browns +10.5 (-122) vs. Buffalo Bills – Iain MacMillan

The Cleveland Browns' run defense has arguably been the best in the NFL this season. They rank third in opponent rush EPA and first in opponent success rate, and are allowing only 3.9 yards per carry. If that holds true in this game, they have a chance to keep things close with the Buffalo Bills.

41.58% of the Bills' offensive yards come from running the football, the fourth most in the NFL. If they struggle to get the ball moving on the ground in Cleveland, the Browns may be in this game longer than people expect.

I also struggle to lay this many points on a Bills team whose defense has been bad all season long, ranking 23rd in both defensive DVOA and opponent yards per play, allowing 5.6 yards per snap.

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Odds refresh periodically and are subject to change.

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