The evening slot for Week 4 features some big-time geographical rivalries — hello Florida/Miami and Washington/Washington State — along with Deion Sanders and Colorado in action, plus a huge Big Ten showdown between No. 9 Illinois and No. 19 Indiana.
Our college football experts have a best bet for those games and more to wrap up the week, so read on to see our favorite college football picks and analysis!
| Game | Time (ET) Network |
Best bet |
|---|---|---|
 vs  |
7:00 | ESPN | Coleman long rec o25.5 -112 |
 vs  |
7:30 | ABC | -7.5 -108 |
 vs  |
7:30 | NBC | -6.5 -114 |
 vs  |
7:30 | FOX | ML +114 |
 vs  |
7:30 | CBS | -20.5 -102 |
 vs  |
10:15 | ESPN | -13.5 -114 |
 vs  |
11:00 | FOX | +18.5 -110 |
CFB Week 4 preview with Andrew Caley and Douglas Farmer
College Football Week 4 Preview with Douglas Farmer and Andrew Caley https://t.co/Fy2bCleATH
— Douglas Farmer (@D_Farmer) September 17, 2025
South Carolina vs Missouri best bet
The South Carolina secondary struggling is probably the thing I’m most convinced about in a game full of uncertainties. Coming into this matchup, the Gamecocks rank in the bottom fourth percentile in pass explosiveness allowed, with almost 14% of the completed passes against them classified as explosive or passes of 20+ yards.
See our full analysis and Gamecocks/Tigers SGP in our South Carolina vs. Missouri predictions.
Florida vs Miami best bet
The Miami defensive line is filled with NFL talent and will be a handful for a struggling Florida offense. Gators QB DJ Lagway has looked overwhelmed through the first three games of the season; he's thrown for just 4.6 yards per attempt and has more interceptions than touchdowns. As a result, the Gators enter this game 1-2 and 99th in offensive EPA margin.
See our full analysis and Gators/Hurricanes SGP in our Florida vs. Miami predictions.
Illinois vs Indiana best bet
Illinois’ offense was not moving forward consistently enough in a win over Duke; it was consistent enough to win a game with a +4 turnover margin, but without that gift, this offense may have worries — against one of the most efficient offenses in the country? That worry becomes reason enough to bet against the Illini.
See our full analysis and Fighting Illini/Hoosiers SGP in our Illinois vs. Indiana predictions.
Arizona State vs Baylor best bet
If ASU can get a baseline average performance from QB Sam Leavitt, the run game is among the best in the nation: Ranked Top 5 by PFF, they have already cranked out 28 runs of 10 yards or more. Baylor’s run defense has been a turnstile, currently sitting 124th in rush yards allowed and 81st in tackling. Auburn piled up 300+ yards rushing, while SMU matched them with 163 on the ground.
See our full analysis and Sun Devils/Bears SGP in our Arizona State vs. Baylor predictions.
Washington vs Washington State best bet
I’m usually hesitant to expect a blowout in a rivalry game. This year’s Apple Cup is an exception, however, as the Washington Huskies look like the far superior team and will be highly motivated after last year’s 24-19 upset loss.
See our full analysis and Huskies/Cougars SGP in our Washington vs. Washington State predictions.
Wyoming vs Colorado best bet
The Buffaloes have had success when running the ball for the most part, with an explosive run rate of over 12%. They picked up 146 yards against Georgia Tech, and I expect we’ll see them commit to it here with their struggles at the quarterback position. Wyoming also won't be a threat offensively, with the 90th-ranked offense in terms of EPA/play, according to GameOnPaper, after adjusting for opponents faced — the Cowboys managed just 10 points against an Akron team that surrendered 68 to Nebraska and 31 to UAB.
See our full analysis and Cowboys/Buffaloes SGP in our Wyoming vs. Colorado predictions.
Michigan State vs USC best bet
USC's lone game against a team with a pulse didn’t look so great last week at Purdue: The Trojans won 33-17, failing to cover the 20.5-point spread despite benefiting from a +3 turnover margin that included a 70-yard big man touchdown. It wasn’t an impressive overall performance. Both teams also operate slowly, limiting possessions and making it difficult to win by a wide margin.
See our full analysis and Spartans/Trojans SGP in our Michigan State vs. USC predictions.
Odds are correct at the time of publishing and are subject to change.
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