No. 16 seed UMBC famously beat No. 1 Virginia in the 2018 NCAA Tournament, 74-54. The result was a historic outcome, as it was the first time that a No. 16 seed had ever won a game in the round of 64.
As of 2023, the second round of the NCAA Tournament was the farthest a No. 16 seed had ever gone in March Madness.
There's a tendency for tournament games to be competitive for 40 minutes. When upsets do happen, they're often the result of a few high-leverage plays near the end of the game that ultimately go the underdog's way.
One of the things that made UMBC's upset of Virginia so historic is that the Retrievers thoroughly outplayed the Cavaliers throughout the entire game, as evidenced by the 20-point margin of victory. The result wasn't the result of one or two fluky plays.