Making his debut through the film The Last Witness in 2001, Yoo Jae-myung mainly took the supporting roles in movies and dramas.

[3] Yoo's popularity was raised through one of the highest rated dramas in Korean cable television history,[4] Reply 1988, in 2015, and he later gained the main roles in films and TV series.

From 2016 to 2018, he appeared in critically acclaimed shows such as The Good Wife, Stranger (Secret Forest), and Prison Playbook.

[8] Yoo next co-starred with Lee Sung-min in crime film The Beast, a remake of the French thriller 36 Quai des Orfèvres, premiered in June 2019.

[12] In 2020, Yoo co-starred with Park Seo-joon and Kim Da-mi in the series Itaewon Class,[13] He next starred opposite Yoo Ah-in in a film Voice of Silence,[14] written and directed by a female director Hong Eui-jeong,[15] based on her script which was selected as one of top 12 projects at Venice Biennale College-Cinema 2016/2017.