Yoon Kye-sang debuted with the South Korean boy band Groove Over Dose, better known by the acronym g.o.d, in 1999. The group’s third and fourth albums were a huge success, having sold over a million copies each. He left g.o.d in 2004 and the group went on a hiatus in 2006. They reunited in 2014 and released the album Chapter 8, which topped local music charts. It was also named Album of the Year at the 2014 MelOn Music Awards.

Yoon Kye-sang made his acting debut in the 2004 film Flying Boys, in which he was named Best New Actor at the 41st Baeksang Arts Awards. In 2007, he was nominated for an Excellence Award at the SBS Drama Awards for Crazy in Love. In 2011, he played the title character in the thriller film Poongsan, which earned him Best Actor nominations at the 48th Grand Bell Awards and the 32nd Blue Dragon Film Awards. In 2011, he received an Excellence Award at the MBC Entertainment Awards for his work in the long-running sitcom High Kick 3: Counterattack of the Short Legs. In 2017, he took home several citations for his performance in the action thriller film The Outlaws.

Yoon Kye-sang enlisted for his mandatory military service in December 2004 and was discharged in December 2006. In February 2013, it was confirmed that he was dating actress, gayageum player, and beauty pageant titleholder Honey Lee. They broke up in 2020. In August 2021, he registered his marriage with his non-celebrity girlfriend.