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It's been a challenging 2025 college football season for the Penn State Nittany Lions in nearly every sense of the word, and it's not about to get any easier this weekend when they go up against No. 1 Ohio State. Penn State is coming off a 25-24 loss to Iowa on Oct. 18 in its first game since head coach James Franklin was fired after the Nittany Lions' 3-3 start, including 0-3 in the Big Ten. After falling to 0-4 in the conference, Penn State travels to play at No. 1 Ohio State (7-0, 4-0) and despite the Penn State program being in a state of flux, the SportsLine model has Penn State covering a 21-point spread in its Big Ten parlay this weekend. The model's Big Ten parlay at DraftKings also includes USC to cover over Nebraska, as the Trojans are 6-point favorites in the latest Week 10 college football odds at DraftKings.

The model simulates every FBS game 10,000 times. Since its inception, it has generated a betting profit of over $2,000 for $100 players on its top-rated college spread football picks, and it enters Week 10 on a profitable 47-33 combined run on money-line and over/under college football picks since the beginning of 2024. Anybody following its college football betting picks at sportsbooks and on betting sites could have seen strong returns.

Three Big Ten betting picks for CFB Week 10 (odds subject to change): 

  • Penn State (+21) vs. Ohio State (-115)
  • Michigan (-21.5) vs. Purdue (-108)
  • USC (-6) vs. Nebraska (-110)

Combining the model's three picks into a CFB parlay at DraftKings would result in a payout of +587 (risk $100 to win $587).

Penn State (+21) vs. Ohio State (-115, DraftKings)

The post-James Franklin era didn't start well with a 25-24 loss to Iowa, but Penn State covered the spread as 3-point underdogs in that contest. With more time to regroup following Franklin's firing and coming off a bye week, Penn State should be in a better position as a program this week. However, they are playing the No. 1-ranked, undefeated Ohio State Buckeyes, which is a significant challenge. Ohio State has won eight straight games against Penn State, but none of those wins came by at least 21 points, as the model projects the Nittany Lions hang tough with Ohio State. The model projects Penn State to cover in 71% of simulations in a 12 p.m. ET start on Saturday.

Michigan (-21.5) vs. Purdue (-108, DraftKings)

The No. 21 Wolverines are 6-2 this season, including 4-1 in the Big Ten, and they are coming off back-to-back conference victories. Michigan has the No. 13 scoring defense in the nation, allowing 17.4 ppg, and is coming off a 31-20 road win against Michigan State. The Wolverines return to Ann Arbor against Purdue, which is 2-6 and 0-5 in the Big Ten. Purdue lost 56-30 on the road against Notre Dame in its only road matchup against a ranked team. Michigan junior running back Justice Haynes rushed for 152 yards and two touchdowns last week, and he's rushed for more than 100 yards in six of seven games this season. His impact is a key reason why the model projects Michigan to cover the spread in 61% of simulations in a 7 p.m. ET start on Saturday. 

USC (-6) vs. Nebraska (-110, DraftKings)

The No. 23 Trojans have dropped two of their last three contests, but both those losses came on the road against ranked opponents and USC is 4-0 against unranked teams in a 5-2 season. Nebraska is 6-2, including 3-2 in the Big Ten, so it hasn't had a poor season, but the Cornhuskers are currently unranked and haven't been ranked higher than No. 25 this season. USC has the No. 2 scoring offense at 42.4 ppm this season, while leading the nation in yards (530 yards per game). Junior Jayden Maiava has thrown for 2,180 yards with 15 touchdowns and four interceptions this season, and he's coming off throwing for 328 yards and two touchdowns with two interceptions in the loss to Notre Dame. He's averaging 311.4 passing yards per game, leading the model to project USC to cover in 60% of simulations in a 7:30 p.m. ET start on Saturday.