NFL Week 10 Upset Predictions & Picks | Biggest Upsets for Week 10

Last Updated: Nov 11, 2021

Week 10 of the NFL season is upon us and the overreactions are loud on the streets. We are officially halfway through the regular season and now have a better idea of which teams are contenders and which are pretenders.

That said, this is still a small sample size of games. Those that have been played can be dug through and sprinkled with context to become useful. Team-adjusted stats like DVOA have some value, and we also have to be aware of how injuries have affected teams to this point.

With that in mind, let’s dive into some NFL Week 10 upset predictions and best bets.

All NFL gameday odds are current as of 3:00 p.m. ET on Thursday, November 11.

NFL Week 10 Upset Predictions

New Orleans Saints vs Tennessee Titans

Tennessee is coming off a major upset last week against the Rams in Los Angeles. Their first game after Derrick Henry’s injury was a roaring success, but not because of their offense. The Titans’ defense generated two interceptions, returned one for a touchdown, and kept Matthew Stafford in hell all night.

Both the pass and run struggled for Tennessee against a top-5 defense, despite finally having a healthy WR room (aka A.J. Brown and Julio Jones). Jones had missed three games this season, but finally suited up for that primetime matchup and looked relatively healthy.

Sportsbook Play of the Day

Before you make your NFL Week 10 Upset bet picks, you should know that Caesars Sportsbook is among the industry’s best, offering an eye-popping array of promotions and matching your first bet up to $1,001 (win or lose) for new signups using our promo code .

Read Chris Wassel’s Caesars Sportsbook review for more insight and get your welcome bonus below, or continue reading this analysis for NFL Week 10 Upset tipster picks.

The Titans now go home to face another top-5 defense, but are favored this time due to New Orleans’ quarterback situation after Jameis Winston’s season-ending injury. Trevor Siemian has stepped in as the starter and been competent thus far, and with Sean Payton coordinating things, that’s all you need. Taysom Hill comes in to mix up the offense and throw teams off, while Siemian plays ball control to move the chains.

The Titans’ defense looks improved, but still ranks 24th against the rush by FootballOutsiders’ DVOA. New Orleans’ strength is its running game and even with a banged-up Alvin Kamara, the Saints can figure things out against a vulnerable Tennessee team.

Upset Prediction: Saints 27, Titans 20

Saints vs Titans Upset Picks

Upset Pick: Saints Moneyline (+125) at BetMGM

The Saints might have just lost to the Falcons, but divisional matchups are always wonky. This was also Taysom Hill’s first game back from a concussion, so he should be much more involved in Week 10.

Taking the Saints with the points at +3 (-115) is not worth betting when this game could wind up as a blowout if Tennessee’s offense repeats last week’s showing.

Upset Pick: Over 44.5 Total Points (-110) at BetMGM

Ryan Tannehill vs Trevor Siemian shouldn’t exactly end up as a shootout, but for the sake of this line, the over can hit assuming the Saints appropriately take advantage of Tennessee’s weakness on defense.

Then, the Titans would be forced into playing catch-up using their top-tier receivers after failing to establish the run early. The Saints’ No. 1 ranked rush defense will be a tough cookie to crack for a team that will need a wholesale philosophical shift.

Trevor Siemian, QB, New Orleans Saints

Saints quarterback Trevor Siemian has proven to be a competent backup in the NFL and will look to make the most of his latest opportunity to start against the Tennessee Titans in Week 10. (Image: USA TODAY Sports)

Philadelphia Eagles vs Denver Broncos

The Eagles and Broncos are a lot closer than their respective records might indicate. Philadelphia is 3-6 while Denver is 5-4 and coming off of an impressive win in Dallas over the Cowboys. Yes, the Eagles are also a week removed from demolishing the Lions, but really, who does that impress?

Head Coach Nick Sirianni has shifted the entire Eagles’ offense in recent weeks to a run-first style. This move was made to not only to protect themselves from Jalen Hurts, but also, to attack opponents’ weaknesses.

Philadelphia’s two most recent opponents, the Chargers and Lions, rank dead-last and 25th in rush defense respectively. Denver ranks 23rd, compared to 15th against the pass, and notably was demolished by Cleveland’s third string running back D’Ernest Johnson not long ago.

Philly’s defense is not exactly impressive, as it ranks mediocrely against both the run and the pass, but the Eagles shouldn’t be overly challenged by a Teddy Bridgewater-led offense.

Upset Prediction: Eagles 24, Broncos 23

Broncos vs Eagles Upset Picks

Upset Pick: Eagles Moneyline (+120) at BetMGM

Credit Denver for trying despite trading away star edge rusher Von Miller, but the Broncos remain flawed and have lost several key pieces in recent weeks, including corner Patrick Surtain II, lineman Graham Glasgow, and linebacker Alexander Johnson.

Tight end Noah Fant was just reactivated from the COVID list, but could be rusty in his return to game action. Backup Albert Okwuegbunam is banged up, making this unit quite thin if Fant has any lingering effects or isn’t 100 percent.

The Eagles come into this contest fairly healthy and have the talent and matchup advantage to boot.

Upset Pick: Over 44.5 Total Points (-110) at BetMGM

I’m going with a sneaky over here, despite both teams relying so heavily on the rush. Denver ranks 29th in Pace, but is offset by a Philadelphia offense that ranks 7th (2nd in neutral situations). Assuming this game stays close, the Eagles will keep their foot on the gas while the Broncos, if forced to play from behind, will be have to play up-tempo and score.

Big play threats are present on both sides of the ball with guys like DeVonta Smith, Dallas Goedert, Jerry Jeudy, and Courtland Sutton.

This game might not end up as boring as it seems on the surface.

Thanks for reading our NFL Week 10 Upset Predictions! For more NFL betting tips, check out our NFL Week 10 Best Bets and NFL Week 10 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.

Related articles


Get $1,500 in Bonus Bets

5 stars

Bet $5, Get $150 in Bonus Bets or First Bet Safety Net

5 stars

Bet $10, Get $200 in Bonus Bets

5 stars

Get A Bonus Bet Up to $1,000

5 stars

Bet $5, Get $200 in Bonus Bets

5 stars

Get A Bonus Bet Up To $250

5 stars

Bet $5, Get $200 in Bonus Bets Every Day for 5 days!

5 stars

If you or someone you know has a gambling problem and wants help, please call 1-800-GAMBLER.

21+ and present in OH. Gambling Problem? Call or text 1-800-GAMBLER (CO, DC, IL, IN, LA, MD, MS, NJ, OH, PA, TN, VA, WV, WY).

Call 877-8-HOPENY or text HOPENY (467369) (NY).

Please Gamble Responsibly. Call 1-800-NEXT-STEP (AZ), 1-800-522-4700 (KS, NV), 1-800-327-5050 (MA), 1-800-BETS-OFF (IA), 1-800-270-7117 for confidential help (MI).

All betting content on is exclusively intended for audience members 21 years and older who are permitted to gamble in legal states. The Game Day may earn revenue from site visitor referrals to betting services.

Responsible Gaming: Many sportsbooks offer ways to encourage responsible gaming, including the establishment of limits to deposits, spending, and time dedicated to betting.

The Game Day is a TGD Marketing Ltd. endeavor.