Oh Jung-se made his silver screen debut in the 1997 movie Father. He then landed his first TV appearance in 2006 through the OCN drama Someday. In 2013, he was cast in his first leading role in the film The Hero. Oh Jung-se received a Golden Acting Award at the 2017 MBC Drama Awards for his work in the mystery thriller Missing 9. He then brought home back-to-back Best Supporting Actor for TV trophies at the 56th and 57th Baeksang Arts Awards for his roles in When the Camellia Blooms and It’s Okay to Not Be Okay. In 2020, he was awarded the Best Character Award at the SBS Drama Awards for the sports series Hot Stove League.

Oh Jung-se is married to his first love Ahn Hee-sun. They dated for almost two decades before finally tying the knot in 2006. They are blessed with two children: a son and a daughter. Oh Jung-se suffers from prosopagnosia or face blindness, which makes it difficult for him to recognize faces. He said in an interview that he had been unable to identify his own son and famous celebrities because of his condition.