Wilkinson's mother died when he was seven, and his father sent him to the Shattuck School in Faribault, Minnesota, where he excelled in five sports and graduated in 1933. He enrolled at the University of Minnesota, where, as a guard and quarterback for head coach Bernie Bierman, Wilkinson helped lead the Golden Gophers to three consecutive national championships from 1934 to 1936. He also played ice hockey for the University of Minnesota. Following his graduation in 1937 with a degree in English, he led the College All-Stars to a 6–0 victory over the defending NFL champion Green Bay Packers in Chicago on August 31.