Lee first gained widespread fame in Korea and some parts of Asia with Boys Over Flowers as Gu Jun-pyo in 2009. The role won him several awards, including the Best New Actor award in the category of television at the 45th Baeksang Arts Awards. Lee is noted for his leading role in City Hunter (2011) – in which he was nominated for Most Popular Actor in the category of television at the 48th Baeksang Arts Awards, as well as Outstanding Korean Actor at the 7th Seoul International Drama Awards, and The Heirs (2013), which garnered him another nomination for Most Popular Actor at the 50th Baeksang Arts Awards. In 2015, Lee had his leading role in Gangnam Blues, which was a local box office hit. In 2016, he starred in his first Chinese film Bounty Hunters.

Despite the release of two albums, My Everything (2013) and Song For You (2014), Lee has stated that he does not wish to pursue a singing career. During their respective releases, he embarked on a tour throughout Asia to meet his fans.