Week 4 College Football Best Bets: Conferences Get Real

By Bill Speros Sep 11th, 2025 4:19 PM EDT

The Sooner Schooner rolls into the SEC schedule this week against Auburn. (USA TODAY)

Our Week 4 College Football Best Bets offer a full schedule of Power 5 conference showdowns.

In the SEC, Auburn visits Oklahoma as both teams seek to break through to the conference championship ranks. The same storyline holds in the “Battle Of Columbia” in South Carolina between the (Columbia) Missouri Tigers and the host Gamecocks. In the Big Ten, Illinois visits Indiana. In the ACC, Clemson plays host to Syracuse in a battle for orange supremacy.

State of Florida bragging rights are on the line at Hard Rock Stadium. There, the Florida Gators come off a visit to “Death Valley” to face the sort-of-hometown Hurricanes. Fans following the action can explore the latest odds and insights through sports betting platforms this season.

Notre Dame and Purdue tussle for their own piece of Hoosier bragging rights.

Other Week 4 College Football Best Bets include:

• Multiple Big 12 Conference Games
• Oregon and Oregon State fight for the Platypus Trophy
• Meanwhile, No. 1 ranked Ohio State and & No. Penn State are off

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Week 4 College Football Best Bets

Here are our Week 4 College Football Best Bets to back on the best sports betting sites. 

Date	Matchup	Week 4 Best Bets	Odds	Book
Fri., Sept. 19	Iowa at Rutgers	TBD	TBD	TBD
Sat. Sept. 20	SMU at TCU	TCU -4	-110	DraftKings
Sat. Sept. 20	Oregon at Oregon State	TBD	TBD	DraftKings
Sat. Sept. 20	Florida at Miami	Florida +6.5	-110	DraftKings
Sat. Sept. 20	West Virginia at Kansas	TBD	TBD	TBD
Sat. Sept. 20	Arizona State at Baylor	ASU +2.5	-110	DraftKings
Sat. Sept. 20	Illinois at Indiana	Illinois +3	-110	DraftKings
Sat. Sept. 20	Michigan at Nebraska	Nebraska +1.5	-110	DraftKings
Sat. Sept. 20	Auburn at Oklahoma	Auburn +4.5	-110	DraftKings
Sat. Sept. 20	Purdue at Notre Dame	Purdue +30.5	-110	DraftKings
Sat. Sept. 20	Michigan State at USC	USC -14.5	-110	DraftKings

Week 4 College Football Best Bets: Game-By-Game Analysis

Friday, September 19

Iowa at Rutgers, 7:30 p.m. (FOX)

Buzz: The Hawkeyes leave the plains of the Midwest and head for the Big Apple, but have to settle for SHI Stadium in Piscataway, New Jersey. Rutgers performed well in sweeping its MAC opponents. Iowa beats up on UMass this week before squeezing out a road win in the Garden State.

Best Bet: TBD DraftKings via OddsJam  

Saturday, September 20

SMU at TCU, Noon (TBD)

Buzz: Another intrastate battle that is stuffed early into the season in the Power 5 expansion era. The Mustangs ran wild as rookies in the ACC last season. TCU earned a national following for dismantling Bill Belichick and the UNC Tar Heels in Week 1. SMU will be outclassed here on both sides of the line.

Best Bet: TCU -4 (-110) at DraftKings via OddsJam  

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Oregon State at Oregon , TBD

Buzz: Oregon more than doubled a 28-point line in beating Oklahoma State 69-3 in Week 2. The Ducks carried a 27.5-point line into Evanston this week. All the talk of the Platypus Trophy can’t make this one palatable.  

Best Bet: TBD DraftKings via OddsJam  

Florida at Miami, TBD

Buzz: The Gators and Hurricanes take their intrastate rivalry to South Beach – well, 20 miles away from South Beach. The Gators visited LSU in Week 3. The Gators cover here in spite of Billy Napier.

Best Bet: Florida +6.5 (-105) at DraftKings via OddsJam  

West Virginia at Kansas, TBD

Buzz: A pair of Big 12 Charlie Browns hope Lucy doesn’t pull away the football. Rich Rodriguez and the Mountaineers spun their wheels in a loss at Ohio before facing Pitt. The Jayhawks spend their off-week absorbing a 42-31 loss they suffered at Missouri.  

Best Bet: TBD at DraftKings via OddsJam  

Arizona State at Baylor, TBD (FOX)

Buzz: The Big 12 remains the most competitive conference in college football top to bottom. These early-season matchups matter. The Sun Devils need to right the ship after a disastrous loss in Starkville. And no, we don’t mean Texas State. Kenny Dillingham gets it done,

Best Bet: Arizona State +2.5 (-105) at DraftKings via OddsJam  

Illinois at Indiana, TBD (NBC)

Buzz: With both Ohio State and Penn State off this week, these two wanna-bes get to hog the Midwest Big Ten spotlight. Indiana owned one of the top records ATS in all of FBS last season. The Illini have yet to earn any respect from oddsmakers this year. And this is their best chance to make an impression in the Big Ten given that they don’t play Oregon, Michigan and Penn State this season. (They play host Ohio State on Oct. 11.) Illinois had a -2 number before beating Duke 45-19. Given the likelihood of a very close outcome here, take Illinois and the 3 points.

Best Bet: Illinois +3 (-110) at DraftKings via OddsJam  

Michigan at Nebraska, 3:30 p.m. (CBS)

Buzz: This is the sort of game that screams “college football Saturday.” The Wolverines got run over by the Sooner Schooner in Week 2 and get Central Michigan this week to find their footing. The Cornhuskers get to flex their defense at home against Michigan freshman QB Bryce Underwood. That’s where the edge lies here. Nebraska’s veteran roster and defense wins the turnover battle and carries the day as home underdogs.  

Best Bet: Nebraska +1.5 (-110) at DraftKings via OddsJam  

Auburn at Oklahoma, 3:30 p.m. (ABC)

Buzz: It didn’t take long for a game like this to have all the earmarks of a potential SEC classic. The Sooners hold the early edge, especially coming off that win over Michigan. Both teams will be undefeated as they open their conference schedule. OU coach Brent Venables, new QB John Mateer and new OC Ben Arbuckle won’t have much space to make a splash. QB Jackson Arnold and RB Jeremiah Cobb Tiger hold onto the ball or the Tigers leave Norman without wagon wheel tracks on their back.

Best Bet: Auburn +4.5 (-110) at DraftKings via OddsJam  

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Purdue at Notre Dame, 3:30 p.m. (NBC)

Buzz: It might be worth taking Purdue at this number before Purdue plays USC in Week 3. Anything resembling a respectable performance could push this under 4 touchdowns. The Irish come off a season-opening loss at Miami and a visit to College Station and Texas A&M Saturday.

Best Bet: Purdue +30.5 (-110) at DraftKings via OddsJam  

Michigan State at USC, 11 p.m. (FOX)

Buzz: Once upon a time, a game with these teams would conjure up visions of a Rose Bowl showdown. This time, we get just another lower-tier Big Ten matchup. USC combined for 132 points in its first two games. Rob Ryan’s defense further tunes-up against Purdue in Week 3. Another Thermopylae for the Spartans.

Best Bet: USC -14.5 (-110) at DraftKings via OddsJam  

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