Kwon Sang-woo started out as a model before making a brief appearance in MBC’s Delicious Proposal in 2001. That same year, he made his big screen debut in the martial arts film Volcano High. In 2002, he won the New Star Award at the SBS Drama Awards for We Are Dating Now. In 2003, he starred in the romantic comedy film My Tutor Friend, opposite Kim Ha-neul. He was named Best New Actor at the 39th Baeksang Arts Awards and the 40th Grand Bell Awards for his work in the movie. Also in 2003, he and Choi Ji-woo led the hugely popular SBS romantic melodrama Stairway to Heaven. In 2004, he took home several popularity awards for the film Once Upon a Time in High School. In 2010, he became part of the main cast of the SBS political drama Daemul, in which he bagged a Top Excellence Award at the SBS Drama Awards. In 2017, he acted alongside Choi Kang-hee in theKBS2 series Mystery Queen and reprised his role for its second season that aired the following year.

In 2006, Kwon Sang-woo filed a complaint against a former gang boss for threatening to turn his house into a sea of blood after he failed to hold a fan meeting in Japan. In September 2008, the actor married actress and former Miss Korea Sohn Tae-young. Their first son was born on February 6, 2009. They welcomed their second child, a daughter, on January 10, 2015.