Graham’s first game for the Northwestern Wildcats football team was on October 4, 1941, when he caught a Kansas State punt and returned it 90 yards for a touchdown. He ran and passed for two more touchdowns in the 51–3 victory. After scoring another pair of touchdowns in a win against Wisconsin, Graham passed to his wide receivers for two touchdowns in a victory over the Ohio State Buckeyes, coached by Paul Brown, the Buckeyes’ only loss of the 1941 season. Northwestern ended the year with an 11th-place showing in the AP Poll of the best college teams in the country.

The following year Graham and some of his teammates enlisted in the military but continued to play for Northwestern. Enlistees from other schools also enrolled at Northwestern, where the U.S. Navy had a training station. The 1943 season was a strong one for Northwestern. The team beat Ohio State, the defending national champions, and a good military team at Great Lakes Naval Station. The Wildcats lost to Notre Dame and Michigan, however, and finished the season with an 8–2 record and a ninth-place ranking in the AP Poll. Graham set another Big Ten passing record, was named the conference’s Most Valuable Player, received All-American honors, and finished third in Heisman Trophy voting. By the end of his college career, he held a Big Ten Conference record for passing yards with 2,132.