Jo In-sung started out as a model before transitioning into acting in 1999 through the MBC sitcom Jump. In 2001, he became part of the main cast of the SBS melodrama Piano, which won him the New Star Award at the SBS Drama Awards. He was also nominated for Best New Actor at the 38th Baeksang Arts Awards for his work in the series. In 2003, he joined Sohn Ye-jin and Jo Seung-woo in the romantic melodrama film The Classic. In 2004, he starred in SBS’ Something Happened in Bali, which earned him several acting citations including Best Actor at the 40th Baeksang Arts Awards. He continued his successful acting streak with leading roles in the SBS romantic drama Spring Days in 2005 and the neo-noir action film A Dirty Carnival in 2006. In 2013 and 2014, he took on the male lead roles in the SBS dramas That Winter, the Wind Blows and It’s Okay, It’s Love, opposite fellow A-listers Song Hye-gyo and Gong Hyo-jin, respectively. His performance in the latter scored him the Daesang at the 3rd APAN Star Awards. In 2021, he appeared in director Ryu Seung-wan’s critically acclaimed action drama film Escape from Mogadishu.

Jo In-sung enlisted in the Air Force for his mandatory military service in April 2009. He received an honorary citation from the Air Force chief of staff ahead of his official release in May 2011. He previously dated actress Kim Min-hee. He developed a close friendship with his It’s Okay, It’s Love co-stars Lee Kwang-soo and D.O.