Kam Woo-sung made his acting debut in the 1991 MBC series Our Paradise. In 2002, he bagged a Top Excellence Award at the MBC Drama Awards for the romantic drama Hyun-jung, I Love You. That same year, he made his big screen debut in the erotic film Marriage Is a Crazy Thing, in which he won Best New Actor at the 2002 Korean Film Awards. In 2006, Kam Woo-sung reached a new milestone in his acting career when he starred in the critically acclaimed period film The King and the Clown. The film was chosen as South Korea’s official entry to the 2006 Academy Award for Best Foreign Language Film. It also took home the Grand Prize for Film at the 42nd Baeksang Arts Awards while Kam Woo-sung bagged Best Actor trophies at the Grand Bell Awards and the Chunsa Film Awards. In 2018, he was cast as lead in the SBS romantic melodrama Should We Kiss First. He and his leading lady Kim Sun-ah earned the Daesang at the 2018 SBS Drama Awards for their performance in the series.

In 2006, Kam Woo-sung married actress Kang Min-young in Australia after 15 years of dating.