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Head coach Nick Saban of the Alabama Crimson Tide is featured in our top Alabama vs. Texas A&M prediction.
Head coach Nick Saban of the Alabama Crimson Tide reacts prior to a game against the Texas Longhorns at Bryant-Denny Stadium. Photo by Kevin C. Cox/Getty Images/AFP.

We're trying to nail a fifth straight profitable showing in Week 4 with our trio of college football upset picks based on the top college football odds from our best sports betting apps.

Just two weeks after Colorado shocked TCU as a 21-point underdog, the Buffaloes needed double overtime to avoid being on the other side of the coin as 23-point favorites against Colorado State. And now our Mike Spector thinks a different fate is coming for the Buffaloes in his college football best bets for Saturday while predicting an eruption from Bucky Irving. Branden Schaeffer also takes a look at that matchup in his Colorado-Oregon player props, and Philip Wood believes Shedeur Sanders could struggle.

Only two AP top-25 teams lost in Week 3, including Tennessee, which hasn't won on the road against Florida in 10 straight contests.

Here are our best college football upset picks for Week 4 (odds via our best college football betting sites; Pick confidence is based on a 1-to-5-star scale).

College football upset picks: Week 4

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College football upset predictions

Clemson ML (+110 via DraftKingsCaesars) vs. Florida State ⭐⭐⭐⭐

The ACC cannibalized itself for the last two seasons while not sending a representative to the College Football Playoff. That may happen again if Clemson wins this home matchup.

This is Florida State’s best chance to end a four-game losing streak at Death Valley and a seven-game overall skid in the series (the longest Clemson winning streak in this rivalry). However, the Tigers haven't started 0-2 in conference play since 2010. Their 28-7 opening-week loss to Duke looked terrible at the time, but it should resonate better if the Blue Devils continue to win. And that game could have ended with a vastly different result if Clemson didn't miss two field goals and turn the ball over twice inside Duke's 10-yard line. The Tigers crossed Duke’s 40-yard line six times and came away with seven points to show for it.

Florida State may have been caught in a lookahead spot, but the team didn't perform well in Week 3 while allowing 29 points to a Boston College offense that Northern Illinois and Holy Cross bested through the first two weeks.

Clemson kicker Robert Gunn III missed yet another field goal and an extra point in Week 3, so head coach Dabo Swinney should be more aggressive in manageable fourth-down situations. The Tigers are 4-3 straight up as underdogs since 2016.

This is a four-star play, as much of the Clemson secondary from 2022 is back to square off with Seminoles quarterback Jordan Travis. The unit finished last season in the top 10 in EPA/pass Allowed.

DraftKings and Caesars are the best shops for Tigers backers, as all of our other best sportsbooks are posting +105 or shorter odds.

Ole Miss ML (+235 via FanDuel) vs. Alabama ⭐⭐⭐

Alabama looks completely vulnerable for what seems like the first time during the Nick Saban era. It suffered the school's first double-digit loss in Tuscaloosa earlier this season against Texas, dropping Saban to 28-3 SU against his former assistants. Can Lane Kiffin make it 28-4?

Kiffin’s teams have enjoyed double-digit win seasons in two of the previous four years dating back to his last campaign at Florida Atlantic. His Rebels are averaging 31 points per game against better Crimson Tide defenses than the 2023 unit over Kiffin's first three head-to-head matchups when facing Alabama as the head coach of Ole Miss.

Saban will not be able to rely on out-scoring Ole Miss now that his quarterback situation looks messy. The Crimson Tide’s 17 points against USF were the team’s lowest against an unranked opponent since 2014, and that came against a pathetic Bulls defense that entered the game ranked 128th in SP+. Saban’s teams have finished with two losses in three of the previous four seasons, so why can’t an Ole Miss program that ranks second in the SEC in total offense (526.7 yards per game) and passing offense (349.7 yards per game) hand the Crimson Tide their second loss before October?

FanDuel is posting by far the best odds for underdog backers, as it's the only shop with higher than +225 odds.

Our Phil Wood is looking for this to be a high-scoring matchup in his Ole Miss vs. Alabama prediction for Week 4.

New Mexico ML (+146 via FanDuel) vs. UMass ⭐⭐⭐

Are we sure UMass deserves to be favored over anybody? The Minutemen have averaged fewer than two wins per year over 11 seasons at the FBS level. UMass was the lowest-scoring team in the country during 2022 (12.5 points per game), and it was held to 13 or fewer points nine times. While New Mexico’s offense wasn't much better at 13.1 points per game, UMass’s offense has been worse for a longer period, finishing 126th or worse in Offensive SP+ in each of the last three years.

The Lobos have scored more than 20 points once in their last 23 games against FBS opponents, but we know the Minutemen won't light up the scoreboard. And while New Mexico is coming off a disappointing 27-17 loss to New Mexico State, the school's most significant rival, it held an Aggies squad that entered the week ranked third in rush success and line yards to just 15 first downs.

New Mexico is getting as low as +125 odds at BetRivers, so FanDuel’s +146 odds represent great value in comparison.

College football upset picks made 9/19/2023 at 6:02 a.m. ET.

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