W   10 - 7 

It was the first meeting between the Hawkeyes and Notre Dame. Iowa defeated a Notre Dame team (coached by the legendary Knute Rockne) that had not lost in 3 seasons (20 games). The game was played during a snow and hail flurry.

In the game, Iowa scored first when future All-American fullback Gordon Locke ran one yard for a touchdown in the first quarter. Duke Slater blocked three Notre Dame men on the touchdown, but Anderson was able to get by him. Locke ran over the All-American for the first points of the day. Aubrey Devine kicked the extra point and Iowa led 7–0. Devine also kicked a 33-yard field goal later in the first quarter to put the Hawkeyes up 10–0. That field goal ended up deciding the game.

The only points the Catholics scored came in the second quarter. All-American halfback Johnny Mohardt threw a 30-yard touchdown pass to Ed Kelley. All-American tackle Buck Shaw kicked the extra point, but Iowa still led, 10–7. That ended up being the final score. However, both Iowa and Notre Dame came close to scoring again on several occasions. Both teams advanced to the 5-yard line of their respective opponent in the third quarter, but both were kept out of the end zone. Mohardt missed a 40-yard drop kick in the fourth quarter that would have tied the game. Olympian Gus Desch led Notre Dame to the 7-yard line of Iowa later in the fourth quarter, but the Hawkeyes held again. The game ended at midfield.

Notre Dame coach Knute Rockne, widely regarded as the greatest football coach of all time, made a famous and unprecedented decision before the game. The navy uniforms of his team were too similar in color to the black uniforms of the Hawkeyes, so Rockne decided to use green uniforms instead. This is where the Notre Dame green color originated in later years.

In 1921, Notre Dame was captained by All-American end Eddie Anderson, who later coached Iowa Ironmen team of 1939. It was his only loss as a player. The Catholics were also led by Hunk Anderson, who later coached Notre Dame from 1931 to 1933.

Notre Dame won their next eight games to finish 10–1. They did not give up more than seven points in a game for the rest of the season. The Catholics did not lose again until they were beaten by Nebraska in their final game of 1922. Iowa and Notre Dame did not meet again until 1939.

	1	2	3	4	F
Iowa	10	0	0	0	10
Notre Dame	0	7	0	0	7