Johnny began performing at an early age with Edgar. Johnny’s very first TV appearance was on a local childrens television show that aired in Houston and Beaumont markets called the Don Mahoney and Jeana Claire show. Don Mahoney was a blind singing cowboy/kiddie show host in the Houston area for many, many years. Jeana Claire was his sidekick and a former Louisiana Hayride backup singer. Their show ran in one form or another on Houston television from the early fifties all the into the late ’80’s (albeit reruns on Access Cable). Johnny and Edgar were on Don’s show as boys of about 10 or 12 playing ukelele and singing. Unfortunately, while Don did save some kinescopes of his shows from the fifties, Johnny and Edgar’s duo was not one of them.
His recording career began at the age of 15, when their band Johnny and the Jammers released "School Day Blues" on a Houston record label. During this same period, he was able to see performances by classic blues artists such as Muddy Waters, B. B. King and Bobby Bland.
In 1968, Winter began playing in a trio with bassist Tommy Shannon and drummer Uncle John Turner. An article in Rolling Stone magazine written by Larry Sepulvado helped generate interest in the group. The album Johnny Winter was released near the end of that year. In 1969 they performed at numerous rock festivals including Woodstock. Contrary to urban legend, however, Johnny did not perform with Jimi Hendrix and Jim Morrison on the infamous Hendrix bootleg recording "Woke up this Morning and Found Myself Dead" done at New York City’s Scene Club. He has said, "Oh, I never even met Jim Morrison! There’s a whole album of Jimi and Jim and I’m supposedly on the album but I don’t think I am `cause I never met Jim Morrison in my life! I’m sure I never, never played with Jim Morrison at all! I don’t know how that [rumour] got started."
Winter struggled with a heroin addiction in the early part of his career. After eventually recovering from the addiction, in 1973, he returned to the music scene in classic form with Still Alive and Well, a song written by Rick Derringer saluting Winter for overcoming his addiction.
In live performances, Winter often tells the story about how, as a child, he dreamed of playing with the blues guitarist Muddy Waters. In 1977, he accomplished this goal and produced the Muddy Waters album Hard Again. In 1978, he experienced continued success with the production of Waters’ I’m Ready. He followed this in 1980, by producing Muddy’s final effort, the album King Bee. Their partnership produced a number of Grammy-winning recordings throughout, and he recorded the album Nothing but the Blues with members from Muddy Waters’ band.
There are quite a few Johnny Winter albums that are considered "non-official." A majority of these albums were produced by Roy Ames, owner of Home Cooking Records/ Clarity Music Publishing. According to a Houston Press article dated Aug 28, 2003, Johnny Winter left town for the express purpose of getting away from him. Roy Ames died on August 14, 2003 of natural causes at age 66. As Ames left no obvious heirs, the ownership rights of the Ames master recordings remains unclear.
As Johnny stated in an interview when the subject of Roy Ames came up, "This guy has screwed so many people it makes me mad to even talk about him."