After beginning a career as a Wall Street stockbroker, he moved into public service by volunteering for his community board and working for then-city comptroller Elizabeth Holtzman.

[9] Duane has also served as a member of his local Community Board, and four terms as Male Democratic District Leader in the 64th New York State Legislature.

[citation needed] Only the second openly LGBT member of the New York Legislature, he later became one of six, alongside Assemblymembers Micah Kellner, Daniel O'Donnell, Matthew Titone, Harry Bronson and Deborah Glick.

[14] Duane was the prime Senate sponsor of the state's Gender Expression Non-Discrimination Act (GENDA),[15] which became law in 2019 after he had left office.

Duane's advocacy of this cause was personal as well as principled; in 1983, he was hospitalized after being assaulted by two men shouting anti-gay epithets, yet the perpetrators were charged only with a misdemeanor.

He also took the lead on "Manny's Law", which requires hospitals to disclose to indigent patients the availability of state-sponsored funds for health care costs, and worked to enact a rental cap of 30 percent of income for people who are living with AIDS and eligible for government financial assistance.

[22] In June 2012, Duane announced that he would be leaving the Senate, citing weariness with commuting between New York City and Albany and in general being ready for "another chapter in my life.

[27] In January 2022, Tom Duane endorsed New York State Assembly candidate Tony Simone for the June 28, 2022 Democratic Party Primary.