The 72nd annual edition of the tournament began on March 16, 2010, and concluded with the championship game on April 5, at Lucas Oil Stadium in Indianapolis, Indiana.

[7] In Oklahoma City, Ali Farokhmanesh drilled a three-pointer with 4.9 seconds remaining to lift ninth-seeded Northern Iowa over UNLV.

Buckeye star Evan Turner struggled from the field, shooting 2–13 and scoring nine points, and the Gauchos put up a fight playing from behind most of the game.

The Terrapins beat Houston 89–77 behind a career-high 21 points and 17 rebounds from freshman Jordan Williams,[12] while the Spartans edged New Mexico State, 70–67.

The end of the game included a controversial lane violation call on Aggies player Troy Gillenwater with 18.6 seconds left that allowed MSU to reshoot a missed free throw and extend its lead to 3.

Leading by just one in the final minute of play, Ali Farokhmanesh clinched the victory for the second time in as many games with a three-point basket that ESPN's Pat Forde called "the greatest early-round shot in NCAA tournament history.

Michigan State extended its halftime lead of NINE to 16 in the second half before falling behind by one late after succumbing to Maryland's relentless pressure defense and some spectacular plays by Greivis Vásquez.

[18] In Milwaukee, Ohio State's Evan Turner bounced back from his off-night in the first round, nearly recording a triple-double (24 points, 9 rebounds and 9 assists) as the Buckeyes downed Georgia Tech 75–66.

[19] Michigan State's Durrell Summers, after scoring 80 points on 54 field goal attempts, was named the region's Most Outstanding Player.

It was a close game between Pittsburgh and Oakland in Milwaukee until Grizzlies forward Derick Nelson received an elbow from Gary McGhee of the Panthers, opening a cut over his left eye that began spurting blood.

Jordan Crawford, the Xavier player who made national headlines the previous summer when he dunked on LeBron James during a training camp held by the Cleveland Cavaliers superstar,[28] scored 28 points for the Musketeers, 17 of those came in the second half.

[29] Murray State had another chance at an upset against Butler, but a 3-point play by Bulldog Ronald Nored dashed those hopes, along with Gordon Hayward deflecting a Racers pass.

[30] The Bulldogs' next opponent, top-seeded Syracuse, rolled over Gonzaga, 87–65, with Wes Johnson scoring a career best 31 points and pulling 14 rebounds.

[33] In what Gregg Doyel of CBSSports.com called "one of the best games in the history of the Sweet 16", Kansas State downed Xavier, 101–96, in double overtime in Salt Lake City.

[34] The Musketeers' Terrell Holloway made three free throws with 5 seconds remaining in regulation to pull Xavier even with the Wildcats.

Trailing by four with 5:23 left, Butler held the Orange scoreless for nearly five minutes, while scoring 11 points of their own, including a 3-point shot by Willie Veasley that bounced high off the rim before hitting the backboard and eventually falling through the net.

[36] The West All-Regional team was made of regional MVP Gordon Hayward and Shelvin Mack of Butler, Denis Clemente and Jacob Pullen of Kansas State, and Jordan Crawford of Xavier.

The Longhorns, who had been ranked number one as recently as January, but fell to an 8 seed in the tournament, twice trailed by double digits before rallying, then held an eight-point lead before falling.

[41] Ivy League champion Cornell joined the parade of double-digit seeds advancing to the second round with a dominating performance over Temple, 78–65, in Jacksonville, Florida.

The Missouri Tigers' defense forced 20 turnovers and stole the ball 15 times in the win, while Kim English and Keith Ramsey had 20 points each offensively.

With 18 points from Quincy Pondexter and 15 from Isaiah Thomas and Matthew Bryan-Amaning each, the Huskies played their uptempo style to a 12-point lead at halftime that grew to 23 midway through the second half.

Four players scored in double figures for UK as they built an early cushion, then padded it to 31 points by the second half.

But a talented Wildcats squad spoiled the party after that with 16 points from DeMarcus Cousins, 12 rebounds from Patrick Patterson and 8 assists from John Wall.

[58] Finally, in Spokane, the fourth-seeded Purdue Boilermakers had a go of it with upset specialist Siena, trailing the Saints 32–29 at halftime before racing to a 14-point lead to open the second half.

In a tough, physical game, the Bulldogs, despite going more than 11 minutes without a field goal, were able to hang on after forcing Michigan State into 16 turnovers and holding the Spartans to zero fast-break points.

The highlight of the game came when Nolan Smith missed a contested, fast-break layup, but Kyle Singler and Miles Plumlee combined to slam home the rebound to give Duke a 14-point lead.

With starters Matt Howard and Ronald Nored on the bench in foul trouble, backup center Avery Jukes came up big for Butler.

[66] The second half was played very closely, with neither team taking a lead larger than two points until a Brian Zoubek layup put Duke up 47–43 with 12:27 remaining.

Kyle Singler missed an open jump shot with 36 seconds remaining, giving Butler a chance to take the lead.

[67] Because a made three-point shot would have resulted in a loss for Duke, some pundits criticized Krzyzewski for his decision to have Zoubek miss the second free throw intentionally.