College Football Predictions, Upset Picks Today: Michigan, Mississippi State on Upset Alert?

We are on to Week 4 of college football after last week’s Lane Kiffin Bowl in Oxford, Miss. This week, we have #1 Texas and #4 Ole Miss both on the road vs. other ranked teams. But those are just two of many games on the Week 4 slate with upset opportunities.

Last week, we nailed the Middle Tennessee State upset over Nevada and had North Carolina over Clemson until the final minutes. That followed hitting both predictions in the Week 2 upsets column. Now we move on to Week 4 looking for more upset picks today.

College football’s Week 4 slate has six ranked vs. ranked matchups, the most in a single week since 2023. Saturday will feature the most ranked conference matchups on a single day in AP Poll history, per Yahoo Sports. We are interested in two of them as possible upset spots. 

Below, we’ll break down our college football predictions and best upset picks for today, including #17 Iowa vs. #18 Michigan and #19 Missouri vs. #24 Mississippi State, with spreads and payouts on PrizePicks Team Picks.

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Week 4 College Football Predictions, Upset Picks – Saturday, September 26

This loaded Week 4 slate has plenty of underdogs, but two games stand out as potential college football upset spots on Saturday, September 26.

Iowa and Michigan square off in an undefeated Big Ten battle at 3:30 on CBS, and surprising 3-0 Mississippi State hosts 3-0 Missouri at 7:45 on SEC Network. 

The payouts listed below indicate real-money earnings if a prediction is correct; for example, a 2x on a $100 entry pays out $200. The lower the payout multiplier, the higher the chance of the outcome occurring, according to user picks. 

Iowa vs. Michigan Prediction – College Football Upset Pick Today

Start Time: 3:30 p.m. ET |  TV: CBS

After barely surviving Western Michigan with the second-chance Hail Mary, Michigan knocked off #11 Oklahoma and needed a big second half to pull away from UTEP last week.

The offense remains a major issue for the undefeated Wolverines, who average 27.3 points per game (91st in the country) and are 90th in the nation in rush offense. They run only 59.0 plays per game, ranked 125th, with an EPA/play of +0.183, 70th in the nation, per Fourth Down Data.

Michigan also ranks 85th in offensive success rate and 113th in standard-down success rate. QB Bryce Underwood is only averaging 168 passing yards per game. Now Michigan and Underwood face an Iowa defense that allows an FBS-low 22.9% success rate and forces three-and-outs on 66.7% of opponent possessions against FBS teams. 

The Hawkeyes’ defense is the best in the country in scoring (4.3 PPG) and yards allowed (176.7), allowing 13 total points this season. Granted, two of the games were vs. NIU and Northern Iowa, but they also beat rival Iowa State. The key is RB Kamari Moulton, who Coach Kirk Ferentz is optimistic will play. 

Iowa has also shown an offense this season, averaging 477 yards and 268 rushing yards a game. The matchup could be decided at the line of scrimmage, where Iowa enters averaging 7.4 yards per carry.

This is an early-season test for both teams, but the road team has looked better so far this season.     

Make your Iowa vs. Michigan prediction on PrizePicks now

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Missouri vs. Mississippi State Prediction – College Football Upset Alert Today

Start Time: 7:45 p.m. ET |  TV: SEC Network

Two undefeated, top-25 SEC teams meet in Starkville, Miss., with two exciting QBs: Missouri’s Austin Simmons and Mississippi State’s Kamario Taylor. Missouri is ranked #19 and Mississippi State is #24 in the latest AP poll.l

Simmons is the former Ole Miss starter whose injury led to Trinidad Chambliss taking over. He has a 218.32 passer rating through three games, second in the SEC, and threw for 292 yards and three TDs in a road win at rival Kansas. He struggled last week against Troy, however, throwing for only 91 yards.

Now Simmons faces a Mississippi State defense that ranks in the bottom 10 nationally in both pressures and sacks. In contrast, Missouri ranks second in the country in pass blocking grade, according to PFF.

The Bulldogs’ defense is also 73rd in EPA per pass and allowed South Carolina QB LaNorris Sellers to throw for 282 yards and 2 TDs last week.

Mississippi State entered the season as one of the lower-ranked teams in the SEC — dead last in our rankings — but the Bulldogs have already upset Minnesota and South Carolina on the road. The Bulldogs are in the AP top 25 for the first time since 2022.

Taylor has burst onto the scene with a 196.26 passer rating, 10th-best in the nation, while adding 178 yards on the ground. 

But he now faces a Missouri defense that is second in EPA per pass, fifth in havoc rate (25.4%), and 16th in total defense, allowing only 226 yards per game.

And while the Bulldogs earned the win last week in Columbia, they were down 16-0 early and were out-gained in total yards.

Make your Missouri vs. Mississippi State prediction on PrizePicks now

Make Week 4 College Football Predictions Today on PrizePicks

A full slate of ranked college football games is on tap for Week 4, and with that, there are plenty of chances for upsets in top-tier games as teams get into conference play.

Can Iowa put an end to Michigan’s unbeaten season? Will Missouri be the team that ends the early-season run by the surprising Bulldogs? 

You can make your college football predictions every week of the 2026 season on PrizePicks — including teams to pull off upsets.

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