His parents divorced when he was three, and he lived with his mother in Montreal for most of his youth.

Wainwright was born in Rhinebeck, New York, USA, to folk singers Kate McGarrigle and Loudon Wainwright III. Wainwright is the son of musicians Loudon Wainwright III and Kate McGarrigle, and the older brother of singer Martha Wainwright. Rufus' 10th studio album, Unfollow the Rules, was released on July 20, 2020.

His ninth studio album, Take All My Loves: 9 Shakespeare Sonnets (2016), featured nine adaptions of Shakespeare's sonnets. The double album Prima Donna (2015) was a recording of his opera of the same name. His second live album, Milwaukee at Last!!!, was released in 2009, followed by the studio albums All Days Are Nights: Songs for Lulu (2010) and Out of the Game (2012). In 2007, Wainwright released his fifth studio album, Release the Stars, and his first live album, Rufus Does Judy at Carnegie Hall. Wainwright's third and fourth studio albums, Want One (2003) and Want Two (2004), were repackaged as the double album Want in 2005. His second album, Poses, was released in June 2001. Wainwright's self-titled debut album was released through DreamWorks Records in May 1998. He has also written two classical operas and set Shakespeare's sonnets to music for a theatre piece by Robert Wilson. He has recorded 10 studio albums and numerous tracks on compilations and film soundtracks. Rufus McGarrigle Wainwright (born July 22, 1973) is a Canadian-American singer, songwriter, and composer.

Hallelujah picking guitar