He has served as spokesperson of the Democratic Progressive Party and the chief executive officer of its Policy Research and Coordinating Committee.

Following his December 2018 loss in the Kaohsiung mayoral election, Chen was appointed Vice Premier of the Republic of China by President Tsai Ing-wen.

Chen yielded the vice premiership to Shen Jong-chin in June 2020, and won the Kaohsiung mayoralty in a by-election on August 15, 2020 after previous mayor Han Kuo-yu was recalled.

[8] After Shui-bian's successful presidential campaign, Chen Chi-mai, as a leader of the Justice Alliance faction, supported the proposal of another member to revise the pro-independence guideline.

[11] The proposal was documented in an essay called New Culture Discourse, drafted by DPP legislator Lee Wen-chung of the New Tide faction.

The document was proved too controversial and was attacked within the party as a result, although some members believed that it was only based on the 1999 Resolution on Taiwan's Future.

[12] In January 2005, following the death of former CCP General Secretary Zhao Ziyang, Chen represented the Taiwanese cabinet in delivering a message to the Chinese government.

Chen stated that Beijing should "face the truth about Tiananmen Square... We urge the Chinese government to learn from Mr. Zhao's tolerance and to push for democratic reforms.

[22] Then-premier Frank Hsieh authorized Chen's resignation on September 12, and replaced him with former vice premier Yeh Chu-lan.

[23] After a temporary period of research at the London School of Economics in England, Chen was appointed the deputy secretary-general of the Presidential Office in February 2007.

[26][27] After the DPP chairmanship election in May 2008, chairwoman-elect Tsai Ing-wen announced the appointment of Chen as the deputy secretary-general of the party.

Chen faced fellow lawmakers Chao Tien-lin, Lin Tai-hua, and Kuan Bi-ling in a Kaohsiung mayoral primary held in March 2018, and was named the Democratic Progressive Party candidate for the mayoralty.

Chen's resignation from the vice premiership took effect on 19 June 2020, as he then represented the DPP as their candidate contesting in the 2020 Kaohsiung mayoral by-election scheduled for 15 August.

[33] Following the successful recall attempt against Han Kuo-yu, Chen registered as the candidate representing the Democratic Progressive Party in the 2020 Kaohsiung mayoral by-election on 15 August with many calling on him as the favorite to win.