No. 1 seeds had been 135-0 against No. 16 seeds.
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Chaminade's 77-72 victory over Ralph Sampson and then No. 1-ranked Virginia in 1982 in Hawaii was generally considered the most remarkable upset in college basketball history. But that was a regular-season game.
This came when it mattered the most — in the NCAA Tournament.
Virginia entered the tourney as the No. 1 overall seed after going 31-2 this season, including 20-1 in ACC competition.
Maryland-Baltimore County has an enrollment of approximately 14,000 students.
The Cavaliers couldn't get anything generated on offense and the nation's top-ranked defense couldn't contain the American East Conference champions.
The 74 points were the most Virginia had allowed this year.
Senior guard Jairus Lyles scored 28 points for Maryland-Baltimore County. He diced up Virginia's defense in the second half, getting to the hole easily on six different occasions and making easy layups. He also knocked down a pair of 3-pointers as UMBC built a 16-point lead.
"These are the moments that you dream of," Lyles said.
Lyles scored 23 of his points in the second half.
The game was tied at halftime, but the Retrievers built a double-digit lead that Virginia could never erase.
"Unbelievable — it's really all you can say," UMBC coach Ryan Odom said.
Maryland-Baltimore County will face No. 9 seed Kansas State on Sunday in the second round.
In women’s basketball, the No. 16 seed Harvard women beat top-ranked Stanford in 1998.
The Associated Press contributed to this article.