Han Seok-kyu began his acting career as a voice actor before making his television debut in the 1990 MBC campus drama Our Paradise. In 1994, he took home a Top Excellence Award at the MBC Drama Awards for his portrayal of a gigolo in The Moon of Seoul. In 1995, he appeared in the film Doctor Bong, which won him Best New Actor at the 6th Chunsa Film Art Awards and the 32nd Baeksang Arts Awards. In 1997, he starred in the movie Green Fish, which bagged numerous Best Film trophies. His work in the movie also earned him a couple of Best Actor citations, including one from 33rd Baeksang Arts Awards. In 1998 and 1999, he headlined the successful films Christmas in August, Shiri, and Tell Me Something, which scored him several Best Actor and Popularity Award trophies.

After starring in a series of controversial films in the early 2000s, Han Seok-kyu regained his glory with a leading role in the 2011 SBS sageuk Tree With Deep Roots, which bagged the Daesang for TV at the 48th Baeksang Arts Awards. He also received the Daesang at the SBS Drama Awards for his performance in the series. In 2016, he won another Daesang at the SBS Drama Awards for his portrayal of the titular character in the hit medical drama Romantic Doctor Teacher Kim. In 2020, the series came back for a second season, in which he reprised his role.

Han Seok-kyu sang in an amateur folk rock band while he was attending Dongguk University’s theater and film department. He is a fishing enthusiast. He has been married to his wife since 1998.