NFL Week 16 Upset Predictions & Picks | Biggest Upsets for Week 16

Last Updated: Dec 25, 2021

Week 16 of the NFL season is upon us. Now that we are well into December, we have a much better idea of which teams are contenders and which are pretenders.

With a solid sample size of games to judge teams on, team-adjusted stats like DVOA have a ton of value. We also have to be aware of how injuries have affected teams to this point.

As always, context is key.

With that in mind, let’s dive into some NFL Week 16 upset predictions and best bets.

Please note that all NFL gameday odds and lines are current as of 6:30 p.m. ET on Thursday, December 23.

NFL Week 16 Upset Predictions

Minnesota Vikings vs Los Angeles Rams

If there is anyone who knows the ins and outs of Matthew Stafford, it’s Mike Zimmer and the Minnesota Vikings. Obviously, Stafford’s weapons and protection in Los Angeles are significantly better than his recent years in Detroit, but his tendencies are the same.

These types of things are difficult to quantify, but are often in play for how weird divisional matchups get.

To the Rams’ credit, they are playing a high level of football in December. Their three-game win streak comes with a plus-47 point differential, though 30 of them were against the Jaguars.

This rejuvenation after a three-game losing streak in November comes at the hands of newfound workhorse, Sony Michel, who is a significantly better fit for Sean McVay‘s wide zone scheme than Darrell Henderson.

Additionally, the Rams are benefitting from having Von Miller and Odell Beckham Jr. in the building each day. Switching teams midseason is no easy task, and learning new calls/language along with building chemistry takes time.

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Although Minnesota is down several pieces along the defensive line, they still generating the league lead in sacks per game (3.1). Zimmer is well-deserving of his hot seat due to various reasons, but there is no doubt he is still a very capable defensive mind.

Minnesota is also dealing with the loss of RB Dalvin Cook, but the Vikings are lucky enough to have a pseudo-workhorse in Alexander Mattison and a low-usage speed demon in Kene Nwangwu. This duo can’t fully replicate Cook’s production, but it should be enough.

The hopeful return of WR Adam Thielen should be the biggest boost this team could get as it takes a ton of pressure off of the run game and star WR Justin Jefferson.

Upset Prediction: Rams 23, Vikings 27

Vikings vs Rams Upset Picks

Upset Pick: Vikings Moneyline (+155) at Caesars

Wager: 2 Units

The Rams are a much better team on both sides of the ball than the Vikings are, but with the Rams coming off of a brutal Tuesday matchup against a division rival and heading into Minnesota for a morning game, an upset here would not be shocking.

Upset Pick: Over 49 Total Points (-110) at Caesars

Wager: 1 Unit

Minnesota’s defense is below-average against the rush and through the air, while the Rams are top-10 against both. Unfortunately for the Rams, they are at a disadvantage due to scheduling circumstances, so we may get a skewed look at them on Sunday.

Both teams are in the top-15 of the NFL in pace and should force each other to pass plenty throughout the game with the big play weapons on each side.

Justin Jefferson, WR, Minnesota Vikings

Always a threat to pop, look for Justin Jefferson to have another big game when the Minnesota Vikings host the Los Angeles Rams this weekend. (Image: USA TODAY Sports)

Buffalo Bills @ New England Patriots

This is the first true matchup of the season between these AFC East rivals. Yes, the first actual game does not count at all due to the ridiculous weather conditions that threw both teams for a loop.

Looking at this game in a vacuum, the Bills head into New England as the better team. Though they are back-to-back in defense as the two best teams in the NFL, the Bills’ offense ranks higher despite a virtual lack of a rushing attack throughout the season.

For what it’s worth, the Bills did something last week they haven’t done in seemingly forever, which is give Devin Singletary almost all of the backfield touches.

With Zack Moss inactive over the past two weeks and Matt Breida‘s hype short-lived, Singletary seems to be what gives this team the best chance to win.

Meanwhile, the Patriots are down several pieces, including WR Kendrick Bourne, WR Nelson Agholor, and RB Rhamondre Stevenson. While Stevenson’s absence could be mitigated with New England’s depth, starting RB Damien Harris missed last week’s game due to a hamstring injury.

Upset Prediction: Bills 24, Patriots 17

Bills @ Patriots Upset Picks

Upset Pick: Bills Moneyline (+115) at Caesars

Wager: 2 Units

At the end of the day, Josh Allen is a significantly better QB than Mac Jones and the better side to consider when placing a bet. Yes, he can make costly mistakes, but the benefits overall on offense are what you desire. Jones simply helps a team not lose.

Now down several primary weapons, Jones is going to be asked to do a lot more than he has before and pass much more than the three times he did in this most recent matchup.

Back the Bills here with your NFL bet of the day.

Upset Pick: Under 43.5 Total Points (-110) at Caesars

Wager: 1 Unit

New England ranks No. 25 in pace, while Buffalo ranks No. 14. In neutral situations (either team within six), Buffalo ranks second while New England sits dead-last.

This game is quite curious to peg for the Over/Under, but with both teams dealing with offensive absences while ranking first and second in defense, Under 43.5 is the bet.

Thanks for reading our NFL Week 16 Upset Predictions! For more NFL betting tips, check out our NFL Week 16 Best Bets and NFL Week 16 Prop Bets.


Kev Mahserejian

Kev Mahserejian is an NFL/NBA/MLB analyst at The Game Day, residing in Los Angeles, CA. He graduated from the University of Southern California in 2017 and began creating sports content soon after. Kev currently writes fantasy and betting pieces while also hosting his podcast The Operating Room with various guests from the sports industry to discuss topics primarily regarding fantasy. He also writes for RotoBaller and is quite active on his Twitter @RotoSurgeon.

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