He has been the deputy leader of the Australian Labor Party (ALP) since 2019, having served as the member of Parliament (MP) for the division of Corio since 2007.

In the local ballot Marles polled 57% of the vote, and his endorsement was then confirmed by the party's public office selection committee.

From February 2008 to June 2009 he was chair of the House of Representatives Standing Committee on Aboriginal and Torres Strait Islander Affairs.

He retained his seat in the 2010 election and was sworn in as Parliamentary Secretary for Pacific Island Affairs in the First Gillard Ministry on 14 September 2010.

[8] Marles arrived in Wallis and Futuna to attend a ceremony with King Kapiliele Faupala in Mata-Utu marking the 50th anniversary of the islands' status as a French Overseas collectivity.

After the ALP's defeat at the 2013 federal election, Marles was appointed Shadow Minister for Immigration and Border Protection under opposition leader Bill Shorten.

[15][16] Following a shadow cabinet reshuffle in January 2021, Marles was placed in charge of a new "super portfolio" relating to recovery from the COVID-19 pandemic,[17] encompassing a "broad brief across national reconstruction, jobs, skills, small business and science".

[18] Two days after the 2022 federal election, Albanese had himself, Marles and three other senior Labor frontbenchers sworn in as an interim five-person government.

[13] Marles supports the turning back of asylum seekers who arrive in Australia by boat and a Pacific Solution for the resettlement of refugees.

[21] Marles was supportive of an Australian War Memorial commemorating Operation Sovereign Borders navy personnel who undertook activities to stop asylum seekers coming to Australia by boat.

[22] In 2020, as shadow defence minister, Marles was critical of the Morrison government's handling of the programme to purchase French submarines, which, he said, had "profoundly compromised" Australia's national security.

[23] On an interview on Sky News on 20 February 2019, Marles stated that it would be "a good thing" if the thermal coal market in Australia collapsed.