re: What is the biggest upset in the history of sports?

Miracle on Ice is my pick. The Soviet Union team was a machine that could consistently beat NHL teams, would have been a favorite to win the Stanley Cup had they been an NHL team... and that's considered the highest level of the sport.

For American college upsets, Chaminade beating Virginia in basketball is ahead of anything else. That would be like Indiana Wesleyan beating Alabama in football.