Hetfield was born on August 3, 1963, in Downey, Los Angeles County, California. His family were of English, Irish, and German descent. The father, Virgil Hetfield (a truck driver) and mother, Cynthia (a light opera singer) were devout and strict adherents to Christian Science, and accordingly, much of his young life revolved around religion. In accordance with their beliefs, Hetfield's parents strongly disapproved of medicine or any medical help and remained vigilant in their faith even as his mother began to die of cancer. Her death and his subsequently turbulent relationship with religion are both recurring subjects that have been the focal point of some of Metallica's lyrics (the songs 'Mama Said', 'Dyers Eve' and 'The God That Failed,' are about Hetfield's mother and father, and 'Until It Sleeps' is about cancer, from which both of his parents died).

Hetfield was nine years old when he took his first piano lessons, before taking on his brother David's drums and finally picking up a guitar at the age of fourteen. His main influence was Aerosmith, and he has said that they were the reason why he wanted to play guitar. Other bands such as Black Sabbath, The Beatles, Queen, Led Zeppelin and Thin Lizzy also had a major influence on him. Hetfield formed his first band, Obsession, in his early teens. Composed of the Veloz brothers on bass and drums, Jim Arnold on guitar, and Hetfield providing lead vocals, the band spent plenty of time in the Veloz brothers' garage jamming, with Ron McGovney and Dave Marrs acting as roadies. Marrs and McGovney subsequently joined the band itself when the Veloz brothers quit.

Without a drummer, the rest of the band decided to call it quits. Although it was Mulligan's departure that led to Hetfield searching for a new drummer, it was Hugh Tanner who introduced him to Lars Ulrich, which led to the creation of Metallica.