Week 4 of the 2024 College Football season offers another enticing mix of non-conference games thanks to the major realignment of the so-called Power 4 conferences.

Bettors will be taking a deep look at college football odds with serious interest. College football betting sites have posted lines for multiple games throughout the season.

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The most notable matchup of Week 4 comes in the SEC. Oklahoma plays host to Tennessee. Elsewhere, Southern Cal visits Michigan.

Opportunities abound on sports betting apps. For instance, BetMGM  has posted a healthy slate of point spreads for more than 100 games for the season, including marquee matchups that get one's blood pumping and digital wallets pulsating. 

Take a look at our favorite college football picks for Week 4 of the 2024 season. Team rankings are from the preseason College Coaches Poll.

College Football Week 4 Odds & Spreads 

College Football Week 4 Best Bets

Friday, September 20
Illinois at Nebraska, 8 p.m., (FOX)

Buzz: 🔒 Bookies+ Exclusive

Saturday, Sept. 21  
Marshall at (3) Ohio State, 12 p.m. (FOX)

Buzz: Big Noon Saturday? Seriously? The bye in the new playoff system will be coveted gem come the Holidays. Monster, lopsided wins against cupcakes are necessary. The Buckeyes want to shock viewers watching the other games in the early time slot. 

Pick: Ohio State -39.5 

North Carolina State @ (21) Clemson, 12 p.m. (ABC)

Buzz: 🔒 Bookies+ Exclusive

UCLA at (16) LSU, 3:40 p.m. (ABC)

Buzz: The party is already underway in Baton Rouge. Given the new playoff format, teams need to win big. Style points will matter this time. Look for the Tigers to keep pouring it on here. UCLA opened in the Big Ten last week and got smacked by Indiana 42-13. LSU showed  mettle at Columbia last week, snagging a tough win over South Carolina. Look for the home team to win big here and keep the locals happy. 

Pick: LSU -22.5 Points

(11) Southern Cal at (18) Michigan, 3:30 p.m. (CBS)

Buzz: This is the Big Ten game of the week. It on CBS. We have entered another meta-verse. ESPN's FPI gives the Vols a 71.2% chance to win. The Wolverines were outclassed at home by Texas 2 weeks ago in 31-12 loss. Lincoln Riley's had 2 weeks - plus a full offseason - to prepare for this game. USC will be ready for its B1G opener. The Trojans' rebuild defense smashed in its debut vs. LSU. It will be the story here in Ann Arbor. 

Pick: USC -5.5 points

(6) Tennessee at (15) Oklahoma, 7:30 p.m. (ABC/ESPN)

Buzz: 🔒 Bookies+ Exclusive