Prior to entering parliament he was the South Australian secretary of the Liquor, Hospitality and Miscellaneous Union (LHMU).

He subsequently held the portfolios of Minister for Mental Health and Ageing (2010–2013), Social Inclusion (2011–2013), Housing and Homelessness (2013), Environment and Water (2013), and Climate Change (2013).

After the ALP's defeat at the 2013 election, Butler was a member of shadow cabinet under opposition leaders Bill Shorten and Anthony Albanese.

After the ALP's win at the 2022 Australian federal election, Butler has held the portfolio of Minister for Health and Aged Care and is the Deputy Leader of the House.

[2] His father, a public servant and Vietnam war conscript, was the grandson of conservative South Australian premier Richard Layton Butler and the great-grandson of conservative South Australian premier Richard Butler, but was not politically active himself.

[2] He attended Unley High School, taking a gap year in Italy before enrolling at the University of Adelaide.

[2] In 1992, Butler joined the Liquor Hospitality and Miscellaneous Workers' Union (LHMU) as a legal officer through his connections with Conlon.

[8] He was also noted for his constructive relationship with the Labor Right faction in South Australia, particularly then-secretary of the Shop, Distributive and Allied Employees Association, Don Farrell.

[1] At the age of 23, he was a candidate for ALP preselection in the seat of Ross Smith prior to the 1993 South Australian state election.