Oh Chang-seok made his acting debut in the 2007 film May 18. The following year, he landed his first TV acting gig in the KBS2 series The World They Live In. In 2012, he joined the main cast of the KBS2 daily drama TV Novel: Love, My Love, which won him Best New Actor at the 20th Korea Culture and Entertainment Awards. In 2013, he starred in MBC’s Aurora Princess, which gave him another Best New Actor trophy at the MBC Drama Awards. In 2014, he was nominated for an Excellence Award at the MBC Drama Awards for his work in the hit weekend series Jang Bori Is Here. In 2017, he worked with Ji Sung in the high-rating SBS legal thriller Defendant. In 2019, he led the KBS2 daily drama A Place in the Sun, which scored him Excellence Award nominations at the KBS Drama Awards and the APAN Star Awards.

Oh Chang-seok is in a relationship with model Lee Chae-eun. They were first paired as an onscreen couple in the TV Chosun dating show Taste of Love in 2019.