Lee Byung-heon debuted as an actor in the 1991 KBS2 series Asphalt My Hometown. Some of his early notable works are the films Who Drives Me Crazy and Runaway and the KBS2 drama Son of Wind, which won him Best Actor at the 32nd Baeksang Arts Awards. He then cemented himself as a bankable star by starring in a string of successful films from 1999 to 2001, namely The Harmonium in My Memory, Joint Security Area, and Bungee Jumping of Their Own. In 2003, he acted alongside Song Hye-gyo in the hit SBS series All In, which scored him the Daesang at the SBS Drama Awards and the Best Actor trophy at the 39th Baeksang Arts Awards. In 2009, he made his Hollywood debut in the film G.I. Joe: The Rise of Cobra. That same year, he led KBS2’s big-budget espionage drama IRIS, which gave him another Daesang at the KBS Drama Awards as well as a Baeksang Best Actor trophy. In 2011, he received the Daesang at the 47th Baeksang Arts Awards for the action thriller film I Saw the Devil. In 2015, he appeared in the film Inside Men, which earned him another set of Best Actor awards. In 2019, he was named Best Actor at the 55th Baeksang Arts Awards for his leading role in the top-rating tvN series Mr. Sunshine. He later collected more Best Actor recognitions for his performance in the 2020 political drama film The Man Standing Next.

Lee Byung-heon dated his All In leading lady Song Hye-gyo from 2003 to 2004. In August 2013, he tied the knot with actress Lee Min-jung. In 2014, Lee Byung-heon was involved in a blackmail scandal after GLAM member Dahee and model Lee Ji-yeon demanded him to pay them five billion won. This was in exchange for not releasing a video of the three of them drinking and making lewd remarks. Lee Byung-heon apologized for the controversy while the two women were sentenced to jail.