College Football Week 4 Opening Odds for Every Top-25 Game (Florida Favored vs. Ole Miss, Texas Favored on Road)

Week 4 of the 2026 College Football season features a bunch of top-25 matchups in the SEC, including the No. 1 Texas Longhorns going on the road against the No. 14 Tennessee Volunteers.

That’s one of six games this week with multiple top-25 teams facing off, with four coming between SEC opponents and two between Big Ten squads.

The AP Poll saw a major shake up after Week 3, where Ole Miss upset the LSU Tigers in Lane Kiffin’s return and the Kentucky Wildcats knocked the Texas A&M Aggies off at home, knocking them out of the top 10.

There’s also a few new entrants into the top-25, as the Florida Gators (now No. 21) are undefeated heading into this week’s battle with the Ole Miss Rebels. Florida is favored at home in that contest.

Mississippi State is also in the top-25 with quarterback Kamario Taylor skyrocketing in the odds to win the Heisman Trophy in 2026.

There’s a chance we see a ton of shakeups in the AP Poll after next week’s action, but who is favored to come out with a win?

Here’s a look at the opening odds for every top-25 college football game in Week 4.

Odds via DraftKings Sportsbook

Northwestern vs. No. 5 Indiana Odds, Spread and Total

Spread: Indiana -22.5 (-110)
Total: 49.5 (Over -112/Under -108)

No. 1 Texas vs. No. 14 Tennessee Odds, Spread and Total

Spread: Texas -5.5 (-110)
Total: 57.5 (Over -110/Under -110)

Illinois vs. No. 7 Ohio State Odds, Spread and Total

Spread: Ohio State -27.5 (-110)
Total: 53.5 (Over -110/Under -110)

Sam Houston vs. No. 11 Texas Tech Odds, Spread and Total

Spread: Texas Tech -37.5 (-110)
Total: 54.5 (Over -110/Under -110)

Wake Forest vs. No. 16 Louisville Odds, Spread and Total

Spread: Louisville -13.5 (-110)
Total: 58.5 (Over -110/Under -110)

No. 3 Notre Dame vs. Purdue Odds, Spread and Total

Spread: Notre Dame -27.5 (-115)
Total: 56.5 (Over -115/Under -105)

Oklahoma vs. No. 2 Georgia Odds, Spread and Total

Spread: Georgia -14 (-110)
Total: 45.5 (Over -102/Under -118)

No. 4 Ole Miss vs. No. 21 Florida Odds, Spread and Total

Spread: Florida -2.5 (-110)
Total: 59.5 (Over -110/Under -110)

No. 15 Utah vs. Iowa State Odds, Spread and Total

Spread: Utah -11.5 (-108)
Total: 49.5 (Over -105/Under -115)

No. 17 Iowa vs. No. 18 Michigan Odds, Spread and Total

Spread: Michigan -4.5 (-115)
Total: 39.5 (Over -108/Under -112)

No. 25 Houston vs. Georgia Southern Odds, Spread and Total

Spread: Houston -19.5 (-110)
Total: 55.5 (Over -110/Under -110)

Wisconsin vs. No. 13 Penn State Odds, Spread and Total

Spread: Penn State -9.5 (-115)
Total: 44.5 (Over -110/Under -110)

Central Michigan vs. No. 6 Miami Odds, Spread and Total

Spread: Miami -42.5 (-110)
Total: 54.5 (Over -110/Under -110)

South Carolina vs. No. 8 Alabama Odds, Spread and Total

Spread: Alabama -11.5 (-110)
Total: 53.5 (Over -115/Under -105)

No. 23 Texas A&M vs. No. 10 LSU Odds, Spread and Total

Spread: LSU -8.5 (-105)
Total: 53.5 (Over -110/Under -110)

No. 20 Oregon vs. No. 12 USC Odds, Spread and Total

Spread: Oregon -1.5 (-115)
Total: 62.5 (Over -110/Under -110)

No. 19 Missouri vs. No. 24 Mississippi State Odds, Spread and Total

Spread: Mississippi State -3.5 (-115)
Total: 59.5 (Over -112/Under -108)

Missouri State vs. No. 22 SMU Odds, Spread and Total

Spread: SMU -34.5 (-110)
Total: 59.5 (Over -110/Under -110)

Odds refresh periodically and are subject to change.

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