Nevers played four sports (football, basketball, baseball, and track and field) for Stanford University from 1923 to 1925 and was a consensus first-team All-American in football in 1925. He played professional football in the National Football League (NFL) for the Duluth Eskimos in 1926 and 1927 and the Chicago Cardinals from 1929 to 1931. In 1929, one week after defeating the Dayton Triangles, who were playing in their final game before moving to Brooklyn to embark on their long and tenuous history through the league, he set an NFL record that still stands by scoring 40 points in a single game. In the same game he subsequently set another NFL record by scoring six rushing touchdowns in a single game against the Chicago Bears, a record that remained unequaled until the 2020 season in which New Orleans Saints' running back Alvin Kamara also accomplished the feat, scoring six touchdowns against the Minnesota Vikings on Christmas Day. Nevers also played professional baseball as a pitcher for the St. Louis Browns of the American League from 1926 to 1928 and the Mission Bells of the Pacific Coast League (PCL) in 1928 and 1929.