Yoo Jae-myung made his acting debut in the movie The Last Witness in 2001 and has since appeared in a long list of TV series and films. In 2015, he starred in the hit tvN drama Answer Me 1988, which became one of the highest-rated shows in Korean cable television history. In 2017, he landed a main role in the tvN crime thriller Forest of Secrets, which won the Daesang at the inaugural Seoul Awards and the 54th Baeksang Arts Awards. He was also nominated for the Baeksang Best Supporting Actor for his performance in the series. That same year, he became part of JTBC’s Life, in which he was named Best Supporting Actor at the 6th APAN Star Awards. In 2020, he played the CEO of a food company in the JTBC drama Itaewon Class, which scored him a Best Supporting Actor nomination at the 56th Baeksang Arts Awards. In 2021, he and Yoo Ah-in led the movie Voice of Silence, in which he bagged Best Supporting Actor nominations at the 57th Baeksang Arts Awards and the 30th Buil Film Awards.

Yoo Jae-myung married his long-time girlfriend, who is a theater actress, on October 21, 2018. They have a child together.