In their 16th season under head coach Frank Camp, the Cardinals compiled a 6–3 record and outscored opponents by a total of 180 to 92.
[1][2] Quarterback Johnny Giles set a new school record with 1,346 yards of total offense during the 1961 season.
The team played its home games at Fairgrounds Stadium in Louisville, Kentucky.
[9] His total offense mark ranked eight among the nation's small college players during the 1961 season.
[10] Giles also tied Johnny Unitas' Louisville single-game record with four touchdown passes in a victory over Marshall.