College Football Week 3 Upset Picks: Clemson, Nevada on Upset Watch?

We are on to Week 3 in the college football season after last week’s instant classic between Texas and Ohio State. The top-4 showdown did not disappoint, and the Longhorns took over the top spot in the polls.

This week, our treat is Lane Kiffin’s return to Ole Miss after leaving them before the College Football Playoff run last year. But that’s just one of many games on the Week 3 slate with upset opportunities, as the Rebels seek their revenge.

Last week, we nailed both upsets in this column as FAU knocked off Navy and Duke got revenge for its loss to Illinois last year, winning by four.

CFB Week 3 features the start of conference play for many teams, including one that we will highlight for a possible upset.   

Below, we’ll break down our college football upset picks for Saturday’s games, including UNC vs. Clemson and Middle Tennessee State vs. Nevada, with spreads and payouts on PrizePicks Team Picks.

Pick college football upsets today on PrizePicks — including winners and spreads!

Week 3 College Football Upset Picks for Saturday, September 19

Two games stand out as potential college football upset spots in Week 3. The spreads and winner payouts are listed below, via PrizePicks.

Bill Belichick and North Carolina start ACC play in Clemson vs. the Tigers at Noon, and Middle Tennessee welcomes Nevada to Murfreesboro in a primetime 7:00 p.m. start. 

The payouts listed below indicate real-money earnings if a prediction is correct on PrizePicks; for example, a 2x on a $100 entry pays out $200. The lower the payout multiplier, the higher the chance of the outcome occurring, according to user picks. Payouts are live as of writing, but subject to change.

North Carolina vs. Clemson: Can UNC Pull Off an Upset?

Start time: 12 p.m. ET | TV: ESPN and Disney+

The first North Carolina game of the season got national attention as Belichick’s Tar Heels opened the 2026 season vs. TCU over in Ireland, upsetting the Horned Frogs with a dominating defensive effort. After a bye to come back stateside, North Carolina added its offense to the narrative, piling up 427 yards in a blowout win over FCS East Tennessee State.

Through two games, the Tar Heels are fifth in the nation in scoring defense, allowing only 13 points per game, and have now gone seven straight quarters without allowing a TD. They held East Tennessee State to 255 total yards and a -13.32 Total EPA after shutting down TCU over the final three quarters. 

On the offensive side, QB Billy Edwards, a transfer from Wisconsin, has completed 65% of his passes and has not thrown an INT this season. 

Clemson’s season could not have gotten off to a worse start, getting blown out of Baton Rouge, 51-10, by Lane Kiffin and the Tigers. The score was ugly enough, but getting outgained 644-145 and outplayed in every facet of the game was the story.  

Week 2 was a win, but only 22-7 over the Sun Belt’s Georgia Southern. Starting QB Christopher Vizzina was injured during his second straight poor start and is doubtful to play this week. The Tigers converted only 2 of 13 third downs and scored one TD on five red-zone trips. Facing the North Carolina defense is not the answer to Clemson’s issues. 

When the teams met last year, a desperate 1-3 Clemson team shell-shocked North Carolina with a 28-point first quarter in a 38-10 victory, and Belichick will remember that one.     

Make your North Carolina vs. Clemson picks on PrizePicks now

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Nevada vs. MTSU: Nevada on Upset Watch?

Start time: 7 p.m. ET | TV: ESPN+ (streaming)

Just like last week’s FAU/UNLV pick, we are playing a Group of Six game with travel considerations. 

Nevada lost at home by two TDs to FCS Montana State, still doesn’t have its starting QB Carter Jones due to injury, and now travels across a couple of time zones to face Middle Tennessee State as a favorite.

Neither backup QB played well vs. Montana State, combining for 167 passing yards, completing only 52.8% of their passes. The Bobcats are the defending FCS champions, but the Wolf Pack were dominated after falling into an early 10-0 hole.

Middle Tennessee State held a fourth-quarter lead last week at Marshall, looking for a 2-0 start. A poor final quarter and a missed two-point conversion in the closing seconds took care of that idea. 

With Nevada having QB issues, it’ll be up to the Blue Raiders to stop the Wolf Pack ground game.

Per PFF, the Blue Raiders are top 30 in the country in tackling, which should force Nevada into throwing downs. That did not work out for them last week vs. Montana State. 

Make your Nevada vs. Middle Tennessee State picks on PrizePicks now

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Make Week 3 College Football Upset Picks on PrizePicks

A full slate of college football games is on tap for Week 3, and with that, more chances for upsets.

Can Bill Belichick and the Tar Heels move to 3-0 and send Clemson to another 1-2 start? Will Middle Tennessee State take care of business at home as a small underdog?  

You can make your college football predictions every week of the 2026 season on PrizePicks — including teams to pull off upsets.

Pick More or Less on player stats, or pick game winners, spreads, and totals to earn real money if you're right! In eligible states, combine Team + Player picks for bigger payouts.

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