The first massive upset of the NCAA Tournament arrived on Thursday as the 15-seed Princeton Tigers knocked out the two-seed Arizona Wildcats 59-55.

Incredibly, the undersized Tigers won despite shooting only four-of-25 (16 per cent) from three-point range, getting it done on the defensive end as they held Arizona to 24 points in the second half.

Despite the loss, it was still a strong showing from the game's top NBA prospect as Arizona's six-foot-11 Lithuanian junior Azuolas Tubelis posted 22 points (nine-of-20 shooting), five rebounds, four steals and a block.

In a full-circle moment, Princeton head coach Mitch Henderson was drenched during post-game celebrations. The victory came 27 years after he played in the Tigers' last great March Madness upset, knocking off four-seed UCLA in the 1996 tournament.

But Arizona were not the only big favourite to fall, as the four-seed Virginia Cavaliers were stunned late in a 68-67 defeat at the hands of the 13-seed Furman Paladins.

Virginia led by four with just 12 seconds remaining, but after two Furman free throws, fifth-year senior Kihei Clark inexplicably tried to launch a full-court pass while being trapped in the backcourt. The pass was intercepted, allowing Garrett Hein to set up J.P. Pegues for the game-winning three with two seconds on the clock.

Things were less dramatic for the one seeds in action, as freshman star and likely NBA lottery pick Gradey Dick led the Kansas Jayhawks to a 96-68 drubbing of the Howard Bison.

Dick, 19, had 19 points (seven-of-13 shooting) with 11 rebounds, five assists and three steals as Kansas kept their foot on the pedal right to the end, using the blowout as an opportunity for some live practice against competitive opposition.

It was a different strategy for the Alabama Crimson Tide, with none of their starters playing more than 21 minutes, including top-three NBA draft hopeful Brandon Miller as he finished scoreless on five shots.

The Houston Cougars completed the one seed clean sweep as they were made to work for a 63-52 win against the Northern Kentucky Norse, with top prospect Jarace Walker putting together 16 points (six-of-eight shooting), six rebounds and two blocks.