Seo Ji-seok debuted as an actor in 2001 with an episode of KBS channel’s Drama City. In 2005, he landed his first big screen role in director Kim Ki-duk’s film The Bow. In 2006, he starred alongside Gu Hye-sun in the hit KBS1 daily series Pure in Heart, which won him Best New Actor at the KBS Drama Awards. In 2010, he joined the main casts of MBC’s Gloria and SBS’s OB-GYN. In 2011, he led the cast of the tvN series Manny. He then became part of the 2011 MBC sitcom High Kick: Counterattack of the Short Legs. In 2015, he worked with Choi Jung-won in the SBS daily drama The Three Witches. In 2019, he replaced Kang Ji-hwan as the main lead in TV Chosun’s time-traveling sageuk comedy Joseon Survival Guide.

Seo Ji-seok attended the Seoul Institute of the Arts. He enlisted as an active-duty soldier for his mandatory military service in May 2007. He was discharged in May 2009. In 2013, he tied the knot with a florist.