Best NFL Parlay Picks for Week 16: Our Top Bets for the Weekend

1. Bills vs. Browns +10.5 (-115)

Buffalo’s five straight touchdown drives helped them secure a comeback win over New England last week and kept the Bills’ hopes of winning the AFC East alive. The Bills face a much easier matchup this week against the Browns.

The two best rookie RBs in football are TreVeyon Henderson and Quinshon Judkins pic.twitter.com/z6516HYokT

— Pats Planet 🪐 (@PatsPlanet_) December 18, 2025

Josh Allen and company are favored by 10.5 points in Cleveland. Buffalo is rightfully a heavy favorite, but the Bills have been victims of trap games before. The natural letdown after last week’s emotional win will also be a major hurdle for the team to overcome.

Cleveland also has the tools it needs to exploit the Bills’ biggest weakness, which is their run defense. Quinshon Judkins leads all rookie running backs with 805 yards on the ground, including 718 yards after contact.

If the Bills cannot tackle Judkins, the rookie could have a career game this weekend. A strong performance on the ground will be enough for the Browns to cover the 10.5 points at home this Sunday.

2. Panthers to beat Buccaneers (+130)

Carolina is a home underdog in the first of their two meetings with Tampa Bay over the final three weeks. The Panthers are getting 3.0 points, but I think they can win outright against the struggling Bucs.

Tampa Bay has lost six of its last eight games. The Panthers have also struggled to string together wins, but Carolina is 4-2 at home this season. In their previous home game, the Panthers outdueled the Rams for a major upset win.

Carolina’s best weapon is its running game. However, the pressure will be on Bryce Young this weekend to take advantage of the Bucs’ porous pass defense.

The Buccaneers have a top 10 run defense, allowing just 101.4 YPG on the ground. However, Todd Bowles’ defense allows 246.9 passing YPG, third-most in the NFL. If Young can recreate his performance from the Rams’ game this weekend, he will lead the Panthers to the upset win.

3. Patriots to beat Ravens (+140)

Another underdog that can add considerable value to your parlay this week is New England. The Patriots’ loss last week ended their 10-game winning streak and prevented them from clinching the AFC East.

New England is a 3.0-point underdog on the road against Baltimore. The Ravens have been up and down all season, as their 7-7 record indicates.

A day after he missed practice, Lamar Jackson returned in full to today’s practice. pic.twitter.com/k1Kzb1UYuf

— Adam Schefter (@AdamSchefter) December 18, 2025

One of the reasons for Baltimore’s struggles is Lamar Jackson’s health. The two-time former MVP missed time earlier this season with a hamstring injury and has not had a full week of practice in over a month.

The Ravens’ defense has also struggled at times. Baltimore has allowed 245+ passing yards in eight games this season. They have also allowed 100+ rushing yards nine times in 14 games.

New England has a well-rounded offense that can exploit whatever the Ravens’ defense is willing to give up. The Pats will win and move one step closer to claiming the AFC East title.

4. 49ers to beat Colts (-270)

San Francisco controls its own destiny in the NFC West title race. Currently, the Seahawks (11-4) have a slight lead over the Rams (10-5) and 49ers (10-4) after Seattle’s win over LA on TNF. However, if the 49ers win out, including a home date with the Seahawks in Week 18, then San Fran will win the conference.

Before the 49ers can order their division championship shirts, they must win their next two games, starting with the Colts this weekend. Indianapolis was one of the hottest teams in the first half of the year, starting 7-1, but they have fallen apart recently.

BREAKING: With the #Seahawks win over the Rams, the #49ers can win the NFC West AND secure the NFC’s No. 1 seed if they win out 🤯 pic.twitter.com/qJiISRi3x3

— 49ers & NFL News 24/7 (@49ersSportsTalk) December 19, 2025

The Colts have lost five of their last six and are winless since their Week 11 bye. Poor injury luck at the QB position forced the team to bring 44-year-old Philip Rivers out of retirement to start last week, and the former Chargers’ legend will be under center again this weekend.

Rivers had 120 passing yards in his return, but he put the Colts in position to win. San Francisco’s defense is on par with Seattle’s and will present similar issues for Rivers.

More importantly, the 49ers’ offense will present a bigger challenge for the Colts’ defense. San Fran will win this Monday Night Football matchup, putting them within striking distance of a late run at the NFC West title.