With plenty of upsets and surprises already as we sit entering Week 4 of the 2021 college football season, who knows what is on tap Saturday. Three straight weeks of unpredictable finishes and top-25 upsets have set the stage for what should be a thrilling remaining three quarters of the season. That action continues Saturday with a number of top-tier matchups across the country. 

While there are only two games between ranked opponents Saturday, both have the potential to be headline makers. Coincidentally, the games will both be held at neutral sites with four huge programs stepping into NFL stadiums for the afternoon. No. 12 Notre Dame and No. 18 Wisconsin will open the day meeting at Soldier Field in Chicago, while No. 7 Texas A&M and No. 16 Arkansas will square off at AT&T Stadium in Dallas.

Overall, 22 of the teams ranked in the AP Top 25 will be in action throughout the day with featured evening games including Tennessee visiting No. 11 Florida and West Virginia taking a trip to No. 4 Oklahoma. To keep tabs on all the action, be sure to check out our Viewer’s Guide and get your remote ready. 

While winning is all that matters for the standings, we care about whether these teams will cover their spreads. Be sure to stick with CBS Sports throughout the day for college football coverage from the opening kickoff on Saturday to the final whistle. Let’s take a look at our expert picks for the fourth full Saturday of the season.

Odds via Caesars Sportsbook | All times Eastern

No. 12 Notre Dame vs. No. 18 Wisconsin

Latest Odds:

Wisconsin Badgers
-6.5

Noon | Fox, fuboTV (Try for free) — Not only do I think Notre Dame covers the spread on Saturday, I’m picking it to win the game outright. While the Notre Dame offense has struggled lately, there’s enough talent at the skill positions to trust its ability to bounce back. I don’t have near the same level of faith in the Wisconsin offense right now. We all saw how the Badgers struggled to move the ball against Penn State in their first game of the season, and Notre Dame’s defense is just as stout. Wisconsin’s defense will keep the Badgers in the game, but unless it forces multiple turnovers and possibly a score, I don’t see how the Wisconsin offense scores enough to win the game. Prediction: Notre Dame (+5.5) — Tom Fornelli

No. 7 Texas A&M vs. No. 16 Arkansas

Latest Odds:

Texas A&M Aggies
-5

3:30 p.m. | CBS, CBSSports.com, CBS Sports App — I’ll take the Aggies in a good ol’ fashioned slug fest. They’ll be able to slow down Arkansas’ running game enough to force KJ Jefferson into uncomfortable passing situations, and a few major mistakes will drastically alter the outcome. Zach Calzada will continue his development as a passer, especially off of play-action, and lead this Texas A&M team to a hard-fought win in Jerry World that covers the line. Prediction: Texas A&M (-5.5) — Barrett Sallee

No. 9 Clemson at NC State

Latest Odds:

Clemson Tigers
-10

3:30 p.m. | ESPN, fuboTV (Try for free) — Carter-Finley Stadium can be a great home field advantage for the Wolfpack, and I think the fans will have an impact on yet another edition of this series that will be undecided into the fourth quarter. Clemson’s defense will keep it low scoring, and low scoring games favor underdogs. Prediction: NC State (+10) — Chip Patterson

Which college football picks can you make with confidence in Week 4, and which Top 25 favorite goes down hard? Visit SportsLine to see which teams will win and cover the spread — all from a proven computer model that has returned almost $3,000 in profit over the past five-plus seasons — and find out.

Tennessee at No. 11 Florida

Latest Odds:

Florida Gators
-19

7 p.m. | ESPN, fuboTV (Try for free) — Yes, it was against Tennessee Tech, but the Volunteers found something on defense that looked fundamentally sound for the first time. That bodes well against a Florida attack that will likely employ more zone-read features into the offense. Expect both teams to struggle to move up and down the field. Florida will win, control the game and its defense will shine yet again … but Tennessee will have enough success to cover the 20 points. Prediction: Tennessee (+20) — Barrett Sallee

West Virginia at No. 4 Oklahoma

Latest Odds:

Oklahoma Sooners
-17

7:30 p.m. | ABC, fuboTV (Try for free) — Oklahoma has played both of its FBS opponents within one score, and West Virginia is probably the best opponent on the schedule to this point. To be sure, the Sooners have the ability to turn on the running game and put away any team in the Big 12. It’s unlikely we see that dimension against this West Virginia team, however. For that reason, expect the score to be closer than it should once again. Prediction: West Virginia (+16.5) — Shehan Jeyarajah