Busey started his the entertainment biz profession as a drummer in a group known as The Rubber Band.[citation needed] He performed on a few Leon Russell recordings, credited as playing drums under the names "Teddy Jack Eddy" and "Sprunk", a character he made up when he was part of a nearby television satirical show in Tulsa, Oklahoma, called “The Uncanny Film Festival and Camp Meeting” on station KTUL. For his performances on Uncanny Film Festival, Busey drew on his American Hero,  a pugnacious, know-everything character. When he told fellow actor Gailard Sartain that his character required a name, Sartain answered, "Take three: Teddy, Jack and Eddy;” thus Teddy Jack Eddy was born.

Busey's first film appearance was as a biker in the low-budget “Angels Hard as They Come (1971). Over the next few years, he landed several film roles of similar genre, generally playing a country redneck or a surly, rebellious type role. His gravelly voice, Texas accent, and wide toothy grin often led him to play characters considered psychotic or bizarre. In 1974, Busey made his major film debut with a supporting part in Michael Cimino's action film “Thunderbolt and Lightfoot”, which featured Clint Eastwood and Jeff Bridges. In 1976, Busey was enlisted by Barbra Streisand and her producer/sweetheart Jon Peters to play Bobby Ritchie, street administrator to Kris Kristofferson's character in the film “A Star is Born”. On the DVD analysis of the film, Streisand says Busey was incredible and that she had seen him on a television series and thought that he had the right qualities play the character role.  In 1978, Busey was featured as rock legend Buddy Holly in The Buddy Holly Story with Sartain as The Big Bopper.  This performance garnered Busey the best recognition of his professional career; the part earned Busey an Academy Award nomination for Best Actor and the National Society of Film Critics' Best Actor award. In the film, he changes the verses to the melody "Well All Right" and sings, "We're gonna love Teddy Jack" a reference to his Teddy Jack Eddy persona.

Throughout his acting career, Busey has been known for his personal quotes ala Yogi Berra. While Yogi’s quotes are considered nonsensically funny, Busey’s are edgier. Some notable examples “You know what "FEAR" stands for? It stands for "False Evidence Appearing Real". It's the darkroom where Satan develops his negatives”, “It's good for everyone to understand that they are to love their enemies, simply because your enemies show you things about yourself you need to change. So in actuality enemies are friends in reverse.”, “You know what "SOBER" stands for? It stands for "Son Of a Bitch, Everything's Real"!, “If you take shortcuts, you get cut short.” Sometimes they leave the reader just shaking their head like this post on Twitter; “Running backwards naked through a cornfield at midnight will show you where you've been.”