15 Middle Tennessee over 2 Michigan State, 90-81, 2016 Opening Round
In all honesty, this might’ve been the biggest bracket-buster upset of them all. The 15th-seeded Middle Tennessee upset the 2nd-seeded Michigan State Spartans. Michigan State entered the tournament as the 5th ranked team in the country, and almost everyone assumed they’d be making a deep run in the tournament. According to ESPN, over 33% of people who participated in the site’s Tournament Challenge picked Michigan State to make the Final Four. Despite the fact that it marked the eighth time that a #15 seed beat a #2 seed in the NCAA Tournament, many people believe this game was the biggest opening-round upset in the history of the Tournament.