March Madness Upset Predictions: Pick These 5 Teams in Your NCAA Tournament Bracket

Even in a year where the gap between the top teams and the rest is more significant than ever, we can expect some madness during the first round. That might honestly be the safest bet in sports.

However, identifying which teams will deliver the madness is entirely different. How does one know which 12-seed will make a run before it happens?

Thankfully, my March Madness upset predictions help spotlight some potential Cinderella squads for the 2025 NCAA Tournament bracket as part of our March Madness predictions.

🏀 Best March Madness upset predictions in first round

Here are my five best March Madness upset picks for the first round of the NCAA Tournament with each team's best moneyline odds from our best sports betting sites.

🚨 No. 12 UC San Diego over No. 5 Michigan (+125 via bet365)
🚨 No. 12 McNeese over No. No. 5 Clemson (+275 via DraftKings)
🚨 No. 13 High Point over No. 4 Purdue (+300 via BetMGM)
🚨 No. 11 Drake over No. 6 Missouri (+222 via Caesars)
🚨  No. 11 North Carolina over No. 6 Ole Miss (TBD)

👉 Want more upset picks? Check out our latest college basketball picks.

🚀 Our best upset picks for Round 1

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🚨 No. 12 UC San Diego over No. 5 Michigan ⭐⭐⭐⭐⭐

🗓️ Game info: Thursday, 10 p.m. ET (TBS)
📊 Best odds: UC San Diego +125 via bet365

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It's an upset that is so chalky that it might not even count by the time these two teams face off in the first round. That could scare you off, but there is a reason why UC San Diego over Michigan is such a popular pick.

The Tritons, who won the Big West, haven’t lost a game since Jan. 18. They also have the perfect recipe as an underdog, ranking second in defensive turnover rate (23.2%) and eighth in 3-point frequency on offense (49.6%).

Michigan's turnover rate is 19.8%, which ranks 328th in the nation. The Big Ten tourney winner has been eliminated in the first weekend three times over the past four years, including two first-round upsets. 

Don’t be surprised when the Wolverines follow that trend.

🚨 No. 12 McNeese over No. 5 Clemson ⭐⭐⭐⭐

🗓️ Game info: Thursday, 3:15 p.m. ET (truTV)
📊 Best odds: McNeese +275 via DraftKings

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I’m afraid to admit how much I love Will Wade’s McNeese Cowboys to be this year’s Cinderella team. After all, they are 7.5-point underdogs against the Clemson Tigers in the first round.

The Cowboys have a player capable of putting the team on his back in Quadir Copeland. As a 6-foot-6 wing, he initiates much of the offense. His assist rate of 37.8% ranks 15th in the nation, so keep that in mind for a potential player prop angle this weekend.

The Cowboys were run out of the gym in their first-round matchup against Gonzaga last year, so they are motivated to perform better this time. McNeese’s 72-64 loss to Alabama on Nov. 11 proves that this team might stay in the fight against Clemson.

🚨 No. 13 High Point over No. 4 Purdue ⭐⭐⭐

🗓️ Game info: Thursday, 12:40 p.m. ET (truTV)
📊 Best odds: High Point +300 via BetMGM

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If things go according to my plan, McNeese and High Point will square off in the second round.

The Panthers, who won the Big South, have some high-level talent on their roster. Kimani Hamilton (Mississippi State transfer), D’Maurian Williams (Texas Tech transfer), and Bobby Pettiford (played at Kansas in 2022 and 2022) all come from power-conference programs.

High Point ranks 15th in the country in 2-point shooting (57.4%), which bodes well against a Purdue team that ranks 350th with a defensive 2-point clip of 56.4%. 

Ruh roh, Matt Painter.

🚨 No. 11 Drake over No. 6 Missouri ⭐⭐⭐⭐

🗓️ Game info: Thursday, 7:35 p.m. ET (truTV)
📊 Best odds: Drake +222 via Caesars

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Drake’s chances of an upset will depend on Bennett Stirtz. The 6-foot-4 guard is a legitimate NBA prospect after winning the Missouri Valley Conference Player of the Year award, averaging 19.1 points and 5.7 assists per game.

But Stirtz is about to face immense pressure from the Tigers, who rank 44th in the country with a turnover rate of 20%. If he can take care of the rock, Drake has a shot after losing in the first round in three of the past four seasons.

The Bulldogs rank 10th in the nation in turnover rate (22.1%) and can slow the game to a halt (364th in tempo). This is not an ideal matchup for Missouri.

🚨 No. 11 North Carolina over No. 6 Ole Miss ⭐⭐⭐

🗓️ Game info: Friday, 3:05 p.m. ET (TNT)
📊 Best odds: TBD

This is somewhat cheating because North Carolina has to win its first four matchup against San Diego State on Tuesday as a -185 favorite to face Ole Miss on Friday. 

But I’ve been following the tournament long enough to know to back the team that everyone complained got in on Selection Sunday.

While North Carolina’s resume was underwhelming, the talent is obvious. The Tar Heels are rated the No. 36 team on Bart Torvik. Using the similar profiles tool on that site, North Carolina resembles the 2022 version of this team that made it to the title game.

I don’t believe the Tar Heels have that kind of run in them this year, but their team profile averages 1.3 wins in the tourney. EvanMiya’s analytical website would make North Carolina a 1.2-point favorite against Ole Miss, suggesting this team has a solid chance of notching at least one win.

🏆 What is the biggest March Madness upset in NCAA Tournament history?

Two years ago, No. 16 seed Fairleigh Dickinson pulled off the biggest upset in March Madness history, stunning No. 1 seed Purdue with a 65-58 win in the first round.

The Knights entered as +2000 underdogs but outlasted the top-seeded Boilermakers to become the second No. 16 seed to ever win a game in the NCAA Tournament.

👉 Check out our full list of the biggest March Madness upsets ever.

🏀 March Madness first-round expert picks

• Who will win the South bracket?
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• March Madness upset predictions
• How to predict March Madness upsets?
• What are the most common March Madness upsets?
• What are the biggest March Madness upsets of all time?
• What are the best March Madness buzzer-beaters?

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