Cornell was born and raised in Seattle, Washington and attended Shorewood High School. His parents are Ed Boyle (a pharmacist from an Irish Catholic background) and Karen Cornell (an accountant from a Jewish background). He has two older brothers, Peter and Patrick, and three younger sisters, Katy, Suzy, and Maggie. Peter, Katy and Suzy formed the band Inflatable Soule, a moderately popular band in Seattle during the 1990s. Peter Cornell is now in the band Black Market Radio, which released their debut album entitled Suicide Parlour in 2006. Cornell and his siblings took his mother's maiden name after his parents divorced.

Cornell mentions on the Audioslave – Live in Cuba DVD documentary that he spent a two-year period between the ages of nine and eleven solidly listening to The Beatles after finding a large collection of Beatles records abandoned in the basement of a house. He then suffered from a severe case of clinical depression during his teenage years, rarely leaving