Five upset possibilities in Round of 64

What is March without the Madness? 

Most of the higher seeds will cruise to the second round on Thursday and Friday, but which high-major programs are facing the toughest tests in their tournament opener?

Historically, it is not uncommon for one or multiple 11, 12, or 13 seeds to pull of the upset and bust a whole bunch of brackets.

Let's examine five matchups on your bracket that present a decent chance of an upset. (All odds from DraftKings.)

No. 12 McNeese (+7.5) vs. No. 5 Clemson

The McNeese State Cowboys could give Clemson a test in the opening round. The back-to-back Southland Conference champions are led by a formidable coach in Will Wade, who will be facing off against his alma mater where he started his coaching career as a graduate assistant from 2005-07.

Southland Conference Player of the Year Javohn Garcia leads the team in scoring, but most of the Cowboys’ success has come from the defensive end of the floor. Their athleticism on that end of the floor should keep them in this game, but the question remains if they have enough offensive firepower to hang with the Tigers.  

If you’re looking to bet an upset in the first round, circle this 5-12 matchup, as at least one No. 12 seed has advanced to the second round in 33 of the last 39 NCAA Tournaments. 

No. 13 High Point (+8.5) vs. No. 4 Purdue 

It’s well known that Purdue has had some trouble in the opening round in recent years. It will face another challenge when the Boilermakers square off against the High Point Panthers on Thursday afternoon. 

The Panthers present a dynamic offensive attack ranked 25th in adjusted efficiency by KenPom. Most of the roster has played at a higher level than the Big South Conference, such as First Team All-Big South members Kezza Giffa (14.8 PPG) and Kimani Hamilton (13.4 PPG), who transferred from UTEP and Mississippi State, respectively. D’Maurian Williams, who made the conference’s second team, is a transfer from Texas Tech and also contributes double figures. 

On paper, the roster and metrics match up with high-major opponents, but will they be able to replicate the speed and physicality of a team like Purdue? 

For High Point to pull off the upset, it will need to use its size advantage against a smaller Purdue team and not let Big Ten Player of the Year Braden Smith get downhill in the pick-and-roll. 

No. 13 Yale (+7.5) vs. No. 4 Texas A&M

Another popular No. 13 seed to pull off an upset this year is Yale. The Ivy League Champions are led by one of the best and least-talked about coaches in the country. James Jones has led the Bulldogs to their fourth NCAA Tournament appearance since 2016, highlighted by an upset victory last year against Auburn in the first round.

Even after losing star center Danny Wolf to Michigan in the transfer portal, Yale conquered the Ivy League once again with efficient offensive play and by limiting self-inflicted errors. Sharpshooter John Poulakidas averages 19.2 points per game, and Ivy League Player of the Year Bez Mbeng is a talented, veteran ball-handler that brings a calming presence to the Yale offense.

The Aggies are strong defensively, but the offensive scheme is tough to watch at times. If A&M goes through a cold stretch early in this game, the Bulldogs can gain the momentum necessary to carry them to an upset victory. 

No. 11 Drake (+6.5) vs. No. 6 Missouri 

Surprisingly, No. 11 seeds have fared very well against No. 6 seeds in the first round in recent history. Since 2011, No. 11 seeds are 29-27 in the opening round, with 91 percent of those teams being underdogs against the spread.

The Drake Bulldogs are a good bet to add to the No. 11 seed’s win tally. With All-American Honorable Mention Bennett Stirtz (19.1 PPG) leading this methodical offense (slowest in the nation according to KenPom’s adjusted tempo rating), Drake finished the season 30-3 and won the Missouri Valley Conference.

Drake has already defeated an SEC team this season in Vanderbilt, so it will be confident heading into this tilt with Missouri. However, Drake will run into trouble if Caleb Grill and the Tigers get hot from deep and force Drake to play catch up, something they’re not built to do.

No. 12 Colorado State (-2.5) vs No. 5 Memphis

Colorado State’s Nique Clifford may be a household name by the end of the weekend. Averaging 19 points per game, the senior guard is leading one of the hottest teams in the country (10-game win steak, sixth longest in the country), clinching a tournament bid for his team by defeating Boise State in the Mountain West championship game.

This game falls into the “upset” category because of seeding only, as the Rams are actually favored against Memphis, which will likely be without its No. 2 guard, Tyrese Hunter, who is battling a foot injury. 

Look for Colorado State’s dynamic offensive attack led by NBA prospect Clifford to upset a Memphis team probably seeded higher than it should be.