His mother enrolled him in Southwestern Assemblies of God University in Waxahachie, Texas, secure in the knowledge that her son would now be exclusively singing his songs to the Lord. But legend has it that Lewis daringly played a boogie woogie rendition of "My God Is Real" at a church assembly that sent him packing the same night. Pearry Green, then president of the student body, related how during a talent show Jerry played some "worldly" music. The next morning, the dean of the school called both Jerry and Pearry into his office to expel them both. Jerry then said that Pearry shouldn't be expelled because "he didn't know what I was going to do." Years later Pearry asked Jerry "Are you still playing the devil's music?" Jerry replied "Yes, I am. But you know it's strange, the same music that they kicked me out of school for is the same kind of music they play in their churches today. The difference is, I know I am playing for the devil and they don't."

Leaving religious music behind so far as performing, he paid dues at clubs in and around Ferriday and Natchez, Mississippi. He became a part of the burgeoning new rock and roll sound, cutting his first demo recording in 1954. He made a trip to Nashville around 1955 where he played clubs and attempted to drum up interest, but was turned down by the Grand Ole Opry as he had been at the Louisiana Hayride country stage and radio show in Shreveport. Recording executives in Nashville suggested he switch to playing a guitar, Lewis, even then confrontational, once recalled suggesting to one Nashville producer, "You can take your guitar and ram it up your ass!"