A member of the Democratic Party, Takano became the first gay person of Asian descent in Congress upon taking office.

[2] Takano ran for the United States House of Representatives in California's 43rd congressional district.

[12] During the campaign, Republican State Assemblyman Ray Haynes outed Takano, calling him a "homosexual liberal".

[14][15] In July 2011, Takano announced he would run for the House in the newly redrawn 41st congressional district, established in the redistricting following the 2010 United States census.

In the June 2012 open primary, John Tavaglione, a Republican who sat on the Riverside County Board of Supervisors,[16] ranked first with 45% of the votes.

When Representative Bill Cassidy circulated a draft letter opposing an immigration reform bill in 2013, asking for signatures, Takano marked it up in red pen like a high school assignment and gave it an F, with comments like, "exaggeration – avoid hyperbole.

For his tenure as the chairman of the House Veterans' Affairs Committee in the 116th Congress, Takano earned an "A" grade from the nonpartisan Lugar Center's Congressional Oversight Hearing Index.

[41] After Sanders dropped out of the primaries, Takano endorsed Democratic nominee Joe Biden.

[45] On July 20, 2024, Takano called for Joe Biden to withdraw from the 2024 United States presidential election.