Prior to officially debuting in the 2008 movie Sleeping Beauty, Ji Chang-wook first had an onscreen appearance in the 2006 film Days…, which was followed by a small role in the 2008 KBS2 series You Stole My Heart. In 2010, he played a Korean-American short track speed skater in the top-rating KBS1 daily drama Smile, Dong-hae. His work in the series won him an Excellence Award at the KBS Drama Awards. In 2011, he took home the New Star Award at the SBS Drama Awards for his portrayal of the titular character in the sageuk Warrior Baek Dong-soo. In 2013, he was cast alongside Ha Ji-won in the hit MBC sageuk Empress Ki, which earned him an Excellence Award at the MBC Drama Awards. In 2014, he was paired with Park Min-young in KBS2’s Healer, which scored him two popularity trophies. In 2017, he was nominated for Best New Actor for Film at the 53rd Baeksang Arts Awards for the action thriller movie Fabricated City. In 2017, he bagged a Top Excellence Award nomination at the SBS Drama Awards for Suspicious Partner. In 2020, he received another Top Excellence Award nomination at the SBS Drama Awards for his performance in Backstreet Rookie.

Ji Chang-wook majored in performing arts at Dankook University. He enlisted for his mandatory military service on August 17, 2017. He was discharged on April 27, 2019.