Musso was the son of a coal miner who starred in high school sports in Collinsville, Illinois, and was therefore offered an athletic grant to attend James Millikin University.

His father, who initially planned to pull him out of school after he completed his "primary" education, grudgingly allowed George to attend college.

Musso attended Millikin University and was a standout in football, basketball, baseball, and track.

In 1933, Musso played in the East-West All-Star game, held in Chicago; it was there he first got the attention of George Halas.

Of note, in 1935 as an NFL lineman, Musso played against Gerald Ford of Michigan in the 1935 College All-Star game.