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The Big Ten on CBS will feature a top-20 matchup in Week 4 as the No. 18 Michigan Wolverines host the No. 11 USC Trojans on Saturday for a 3:30 p.m. ET kickoff. The defending national champions were blown out at home by Texas but could get themselves back into the College Football Playoff mix with a run to the Big Ten Championship Game. Meanwhile, USC had a big opening-week win over LSU and then had an extra week to prepare for its first ever Big Ten game after shutting out Utah State 48-0 two weeks ago.

The Trojans are favored by 4.5 on the road in the latest Week 4 college football odds via the SportsLine consensus. That's one of three ranked matchups on the Week 4 college football Saturday schedule, joining No. 6 Tennessee vs. No. 15 Oklahoma (+7) and No. 12 Utah vs. No. 14 Oklahoma State (+1). Before locking in any Week 4 college football picks on those games or others, be sure to see the latest college football predictions from SportsLine's proven model.

The model simulates every FBS college football game 10,000 times. Since its inception, it has generated a profit of over $2,000 for $100 players on its top-rated college football picks against the spread. It is also coming off a profitable 13-9 season on top-rated spread picks and is off to a 4-0 start on over/under picks this season. Anyone who has followed it has seen strong returns!

Now, it has turned its attention to the latest college football odds and Week 4 college football betting lines on the spreadmoney line and over/underHead here to see every pick.

Top college football predictions for Week 4 

One of the college football picks the model is high on during Week 4: UCLA (+21.5) stays well within the spread at No. 16 LSU in a 3:30 p.m. ET matchup on Saturday. When Chip Kelly left UCLA to become the offensive coordinator at Ohio State this offseason, the Bruins acted quickly to promote running backs coach and former UCLA legend DeShaun Foster to head coach. Foster's squad scratched out a 16-13 win in Hawaii to open the season but is coming off a 42-13 drubbing by Indiana to open Big Ten play.

However, LSU hasn't lived up to expectations this season either, losing to USC to open the year, sleepwalking to a 44-21 win over Nicholls and narrowly avoiding an upset loss in South Carolina last week. The Bruins beat the Tiger outright as 1.5-point underdogs in 2021 and have won four of their last five against the SEC. Meanwhile, LSU has failed to cover in its last five September games and the model predicts that trend continues, with UCLA covering well over 50% of the time. See the rest of its Week 4 college football picks here. 

Another prediction: Florida State (-2.5) finally wins and covers the spread against California in a 7 p.m. ET kickoff on Saturday. Finding value is all about getting the right number, and Florida State's brutal start to the season has created a valuable contrarian spot on Saturday night. The Seminoles have certainly been disappointing through their first three games, but they were 17-point home favorites against Boston College just two weeks ago.

Meanwhile, Cal was a 12-point underdog when it traveled to unranked Auburn earlier this month, so this is a drastic adjustment. The Golden Bears are coming off a sloppy performance against a San Diego State team that was playing without its starting quarterback. They committed 12 penalties for 113 yards in that contest, and it will be difficult for them to go on the road and spring an upset with those kinds of undisciplined mistakes. SportsLine's model has Florida State picking up its first win of the season on Saturday, as the Seminoles are covering the spread in over 60% of simulations. See picks for every other game in Week 4 here. 

How to make college football picks for Week 4

The model has also made the call on who wins and covers in every FBS matchup in Week 4, and it's calling for a whopping seven underdogs to win outright. You can only get every pick for every game at SportsLine.

So what college football picks can you make with confidence, and which seven underdogs win outright in Week 4? Check out the latest college football odds below, then visit SportsLine to see which teams win and cover the spread, all from a proven computer model that has returned over $2,000 in profit since its inception, and find out.

College football odds for Week 4

See full Week 4 college football picks, odds, predictions here

Saturday, Sept. 21

North Carolina State at Clemson (-18.5, 44.5)

Florida at Mississippi State (+6.5, 58.5)

Marshall at Ohio State (-39.5, 52.5)

Arkansas at Auburn (-2.5, 56)

USC at Michigan (+4.5, 44)

Utah at Oklahoma State (+1, 54)

Tennessee at Oklahoma (+7, 57.5)

Louisiana-Monroe at Texas (-44.5, 52.5)

Baylor at Colorado (-2, 51.5)

Kansas State at BYU (+7, 49.5)