Best known for playing the titular transgender singer in rock musical Hedwig and the Angry Inch, Oh's acting career spans theater, television and film.

Highly acclaimed for his portrayal of Gong-gil, Oh was awarded Best New Actor by the National Theater Association of Korea for the play's first run in 2000, and he reprised the role four more times in 2001, 2003, 2006, and 2010.

[10] After its run, a sold-out concert featured four of the actors alternating in the lead role, namely Oh, Cho Seung-woo, Kim Da-hyun and Song Yong-jin.

[11] In succeeding years, the rock musical's popularity remained enduring in Korea, attracting other actors to the role in later runs, such as Um Ki-joon, Jo Jung-suk, Song Chang-eui, Yoon Do-hyun, Kim Dong-wan and Park Gun-hyung.

At a press conference, he jokingly talked about shaving his legs again and being banned from his favorite activities like eating meat, working out, and drinking alcohol, but said that the role was "certainly worth the ordeal."

"[10] Besides portraying Hedwig, 2005 was also significant in Oh's career because of his appearance in the critically acclaimed period drama Shin Don set in Goryeo.

The title is ironic, since the story centers on two characters, a high school music teacher (played by Yoo Jun-sang and Im Choon-gil) and a younger man who's recently been orphaned (played by Ryan and Kim Mu-yeol), who live dull, depressing lives, but the only thing that makes them feel alive and gives them joy is music.

Calling it a musical that's "both cheerful and emotionally weighty," Oh said directing made him feel a huge sense of responsibility, fear, and nerves, but he did his best with the actors "to create something.

A stage adaptation of the 1999 film The Harmonium in My Memory set in the 1960s about a 17-year-old sixth grader who develops a crush on a 21-year-old male teacher newly assigned to her village school, Oh had previously starred in the musical's original run in 2008.

Oh had headlined the comedy musical in 2010, playing a nerd who is reborn as a giant green mutant with superpowers, who fights against corruption and environmental pollution.

[22] Oh was praised for successfully transforming into a grotesque, comical character, shedding the gentle image he frequently portrayed in previous musicals and television dramas.

[28] About his supporting turn as a talented but sidelined baseball player in Wild Romance (2012), Oh said, "It's not easy to depict subtle changes in the character's mind.

He starred in the single-episode That Man's Jealous (2006), Transformation (2007), and Spy Trader Kim Chul-soo's Recent Condition (2010), as well as the four-episode series Special Task Force MSS (2011),[30] and The True Colors of Gang and Cheol (2012).

[24][40][41][42] In 2017, it had been reported that Oh Man Suk was in a relationship with a non celebrity, the couple tied the knot in early 2018 and the news was revealed later by his agency in June 2018.