Lee Kyu-han made his acting debut in 1998 with a role in the MBC series Love and Success. He first gained attention in 2005 when he played the heroine’s ex-boyfriend in the hit MBC romantic comedy My Name Is Kim Sam-soon. That same year, he won the New Star Award for his work in the SBS drama Love Needs a Miracle. In 2007, he joined the main cast of the MBC series Que Sera Sera. In 2010, he received an Excellence Award at the MBC Entertainment Awards for the sitcom More Charming by the Day. In 2015, he became a cast member of the second season of the MBC variety show Real Men. Also in 2015, he appeared in the SBS weekend drama I Have a Lover, in which he was nominated for an Excellence Award at the SBS Drama Awards. In 2018, he bagged an Excellence Award at the MBC Drama Awards for his performance in the MBC family series Wealthy Son.

Lee Kyu-han majored in drama at the Kookmin University. He served in the military between 2002 and 2004 for his mandatory conscription.