Born in Washington DC, Vestine was hired to play with the Mothers of Invention in 1965. He quit the Mothers because he wasn't happy with the music he had to play, which was becoming progressively more strange deviating from the simple country blues-based music which he wanted to play.

He then joined Canned Heat as guitarist when the group formed in 1965. During 1969-70 he was replaced by Harvey Mandel. He played in 1967 at the Monterey Pop Festival but did not, as is sometimes assumed, play at Woodstock, as he had already been replaced by Mandel at this point.

Following the death of Alan Wilson in 1970, Canned Heat fired newer members of the band in favour of the original members and in 1971 Vestine re-joined the band.

In his later life, he played with The Vipers in their 1990s reunion tours. In 1991, Jimmy Carl Black contributed to Vestine's Guitar Gangster solo album. Vestine died in October 1997 at the age of 52 from heart and respiratory failure, while touring in Paris, France.