The first College Football Playoff rankings are out, which means we're a month away from Conference Championship Saturday and the selection of the 12-team CFP. There are games now on almost every night of the week, including a couple on Friday we're highlighting with upset potential.
Friday night’s slate is a mix of conference action, which includes games in the American, ACC, Big Ten, Mountain West, and Big 12. A sneaky spot in the American has our attention tonight.
Below, we’ll break down our college football predictions and Friday upset picks, including South Florida vs. East Carolina and Nebraska vs. Illinois, with spreads and payouts on PrizePicks.
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College Football Predictions, Upset Picks for Week 10 – Friday, November 6
Two games stand out as our favorite college football upset spots on Friday, November 6. These underdogs have a payout higher than 2x to win outright on PrizePicks as of writing.
South Florida travels to East Carolina to meet the Pirates at 7:30 p.m. on ESPN2, and Nebraska and Illinois meet in a Big Ten matchup at 8 p.m. on FOX.
The payouts listed below indicate real-money earnings if a prediction is correct; 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.
South Florida vs. East Carolina: College Football Upset Watch Today
Start Time: 7:30 p.m. ET | TV: ESPN2
The South Florida Bulls have won two straight after opening the American Conference season with two losses but need a big road win over 4-4 East Carolina Friday night to stay in the conference title race.
The Bulls enter the matchup as slight underdogs but have a defense that can help them pull the upset. Their defense has been one of the best in the country, ranked 10th nationally in scoring (14.5 PPG), 24th in total yards (306.6 YPG), and 22nd against the pass (178.4 YPG).
South Florida has allowed 10 points or fewer in four of its eight games, including consecutive wins over Kent State (29-2) and UAB (30-10).
It matches up well against an East Carolina offense that has struggled to move the football consistently. The Pirates, also 2-2 in American play, rank 94th nationally in scoring (24.0 PPG), 102nd in total offense (350.5 YPG) and 114th in passing offense (186.5 YPG).
East Carolina has been particularly ineffective on third down, converting just 31.3% of its opportunities, ranking 129th. The Pirates are also 116th in red-zone scoring percentage (76.7%), going up against a Bulls defense that is top-20 in the red zone.
South Florida enters +5 in turnover margin, 21st in the country, while East Carolina is 90th at -2. East Carolina QB Mitch Griffis has thrown 3 INTs over his last two games and has 5 on the season.
On the other side, Bulls QB Michael Van Buren Jr. has yet to throw an INT while accounting for nearly 1,300 yards of offense.
The biggest question for South Florida is the health of Van Buren Jr., as he left last week’s victory over UAB with an injury, with no official word yet on this week’s game. Backup Luke Kromenhoek was more of a rushing threat, going for 92 yards on 15 carries in relief.
South Florida has won five of its previous six trips to Greenville and brings a significant defensive advantage into Friday night's matchup.
Make your South Florida vs. East Carolina picks on PrizePicks now.
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Nebraska vs. Illinois: College Football Upset Watch Today
Start Time: 8 p.m. ET | TV: FOX
It’s been a weird season for Nebraska, which started the season 5-0 but has lost its last three games by a combined 13 points. The Cornhuskers trailed for a total of 8:41 and led for 116:10 in the three-game losing streak; otherwise, they might have appeared in the first CFP rankings.
Now the Huskers travel to Champaign to take on an Illinois team that is headed in the other direction, winning three straight Big Ten games to improve to 3-2 in conference play. The Illini have home-field advantage, are hot at the right time, and are the underdog in this matchup.
Nebraska's offensive struggles have coincided with a sharp decline in QB Anthony Colandrea's production. Colandrea started the season with 13 TDs and only 2 INTs during the 5-0 start, but he's thrown just 2 TDs with 5 INTs during the losing streak.
That includes a 3-INT game in a 7-point loss to Washington, one of which was a pick-six that gave the Huskies a 10-point lead. During the losing streak, Nebraska’s offense has been held to 41 total points after averaging 42.6 during the 5-0 start.
Meanwhile, the Fighting Illini are ninth nationally in fewest tackles for loss allowed (3.13 per game) and 13th in fewest sacks allowed (1.0 per game). That protection is key against a solid Nebraska defense that is eighth nationally in total yards allowed (270.8 YPG) and 14th in scoring defense (15.6 PPG).
Illinois has also been one of the nation's most disciplined teams, ranking sixth in fewest penalty yards per game (35.0), compared with Nebraska's 113th-ranked 69.4 YPG.
Illinois also welcomed back QB Katin Houser last week from a hand injury, and he passed for 223 yards and a TD to help the Illini to their third straight win. WR Collin Dixon ranks seventh nationally with 60 receptions, 11th with 781 receiving yards, and fourth with 10 TD catches.
At home, Illinois is 15-4 under coach Bret Bielema over the last three seasons, including knocking off Oregon 21-10 just two weeks ago. With games against ranked UCLA and Iowa up next, Illinois needs this one to stay in the Big Ten race.
Make your Nebraska vs. Illinois picks on PrizePicks now.
Make College Football Predictions Today on PrizePicks
There are five Friday matchups to get us ready for a full slate on Saturday. Will Illinois keep winning and send Nebraska to its fourth loss in a row? Can South Florida pull off the road upset at ECU?
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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