Week 16 of the 2025 NFL regular season is on the immediate horizon. It’s another busy one, too. Byes are long gone now, so all 32 teams will be taking the field. Yes, we have 16 football games on this mid-December menu – including even 2 on Saturday. Week 16 kicks off with a massive showdown for NFC West supremacy between the Rams and Seahawks. Also on the schedule are Packers vs Bears, Chargers vs Cowboys, Buccaneers vs Panthers, Jaguars vs Broncos, Steelers vs Lions and Patriots vs Ravens.
Make sure you check out our NFL predictions as we add our picks on the side and total for every game throughout the week – and throughout the entire season. Also don’t miss the NFL best bets page for our top picks. For now, let’s break down the NFL Week 16 opening lines and give our best early bet to make.
NFL Week 16 opening lines and odds
Odds available at DraftKings Sportsbook at time of publishing
- Los Angeles Rams -1.5 (-108) vs Seattle Seahawks +1.5 (-112) – Thursday Night Football
- Philadelphia Eagles -6 (-110) vs Washington Commanders +6 (-110) – Saturday
- Green Bay Packers -1.5 (-112) vs Chicago Bears +1.5 (-108) – Saturday
- Buffalo Bills -10 (-110) vs Cleveland Browns +10 (-110)
- Los Angeles Chargers +2.5 (-115) vs Dallas Cowboys -2.5 (-105)
- Kansas City Chiefs -3.5 (-110) vs Tennessee Titans +3.5 (-110)
- Cincinnati Bengals +1.5 (-118) vs Miami Dolphins -1.5 (-102)
- New York Jets +4.5 (-115) vs New Orleans Saints -4.5 (-105)
- Minnesota Vikings -2.5 (-115) vs New York Giants +2.5 (-105)
- Tampa Bay Buccaneers -2.5 (-112) vs Carolina Panthers +2.5 (-108)
- Jacksonville Jaguars +2.5 (+100) vs Denver Broncos -2.5 (-120)
- Atlanta Falcons -2.5 (-105) vs Arizona Cardinals +2.5 (-115)
- Pittsburgh Steelers +7 (-110) vs Detroit Lions -7 (-110)
- Las Vegas Raiders +14.5 (-110) vs Houston Texans -14.5 (-110)
- New England Patriots +2.5 (-105) vs Baltimore Ravens -2.5 (-115) – Sunday Night Football
- San Francisco 49ers -4.5 (-115) vs Indianapolis Colts +4.5 (-105) – Monday Night Football
Best bet for NFL Week 16: Buffalo Bills -10 over Cleveland Browns (-110)
If there is one thing we learned from Week 15, it’s that big spreads are often not big enough. I mean, there are just some horrendous football teams this season. One such team is Cleveland. The Browns are 3-11 and have lost 3 games in a row, including by 18 points to San Francisco and by a 31-3 margin at Chicago this past Sunday. They even lost to the lowly Titans during this stretch. Shedeur Sanders has been better than Dillon Gabriel – but that’s not saying a lot. This club is third-to-last in total offense and only Las Vegas is averaging fewer points per game than Cleveland.
There are also a lot of really good teams this year. One such team is the Bills. They may not be where they want since New England leads the AFC East, but Josh Allen and company are 10-4 and coming off a humongous road win over the Patriots to keep their division-title hopes alive. At the very least, Buffalo is well on its way to another playoff berth. These are simply 2 squads going in very different directions. As such, this is one of those massive, double-digit spreads that still isn’t big enough. Cleveland is 0-3 ATS in its last 3 overall and 2-5 ATS in the last 7 head-to-head matchups.
We’ll have NFL picks for every game in Week 16!
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