Bonamassa was born and raised in New Hartford, NY. His parents owned and ran a guitar shop. As a fourth-generation musician, he recalls knowing he wanted to be a musician as early as age four. With a great-grandfather and grandfather who both played trumpet, and a father who plays guitar, Bonamassa credits his parents with fostering an appreciation of music in his life as early as he can remember. When he was a young child, he would listen to his parents' large record collection. He recalls at age 7, sitting with his parents on Saturdays and listening to Guitar Slim; Bonnie Raitt; Crosby, Stills, Nash, and Young; Eric Clapton; and Jethro Tull. Thus, he sees his music as an amalgam of all the various rock and blues he heard as a child.
He received his first guitar from his father at the age of 4, and by age 7 he was playing Stevie Ray Vaughan and Jimi Hendrix tunes note for note. At the age of 11, during a short period of being mentored by Danny Gatton, he learned such styles as country and jazz as well as Polka. During this time with Gatton, Bonamassa sat in with Gatton's band whenever they played in New York. He first opened for B. B. King at 12 years of age. After first hearing him play, King said, “This kid's potential is unbelievable. He hasn't even begun to scratch the surface. He's one of a kind.” At 14, he was invited to attend a Fender guitar event; during that trip to the West Coast he met Berry Oakley, Jr. Bonamassa and Berry founded the group Bloodline with Miles Davis's son Erin and Robby Krieger's son Waylon. They released one album which produced two chart singles — "Stone Cold Hearted", and "Dixie Peach." He has since played with other music greats including Buddy Guy, Foreigner, Robert Cray, Stephen Stills, Joe Cocker, Gregg Allman, Steve Winwood, Paul Jones, Ted Nugent, Warren Haynes, Eric Clapton, Derek Trucks, and Jack Bruce.