In the final game of the 1921 season, Minnesota lost to Michigan by a 38–0 score. The game was played at Ferry Field in Ann Arbor, Michigan, before a crowd estimated at 33,000 spectators, first in drizzling rain and then in cold weather. Prior to the start of the game, a ceremony was held dedicating a bronze memorial tablet honoring four Michigan athletes who died in World War I.
Michigan's quarterback Irwin Uteritz scored two touchdowns, including a 65-yard interception return that the Detroit Free Press called "the most thrilling achievement of the afternoon." Michigan end Clark Dean added a field goal from the 50-yard line that the Free Press called "the longest of the season, and, in most respects, the greatest any Michigan man ever exhibited to the gaze of paid spectators."Franklin Cappon scored on a 60-yard touchdown run, and Paul G. Goebel kicked all five extra points and, unguarded late in the game, scored a touchdown on a 30-yard pass from Doug Roby that the Free Press called Michigan's "most spectacular pass" since 1907. Frank Steketee also scored a touchdown when he jumped on a Cappon fumble in the end zone. The game marked the worst defeat that a Minnesota football team had suffered to that point in the program's history, exceeding a 41–7 loss to Iowa earlier in the 1921 season.