Lee Dong-wook made his first TV appearances in 1999 after winning a modeling contest. In 2002, he won Best New Actor for TV at the 10th Korean Most Popular Entertainment Awards for the KBS2 series Loving You. This was followed by a New Star Award win at the 2003 SBS Drama Awards for Land of Wine. In 2005, he was launched into Hallyu stardom after taking on the leading role in the hit SBS romantic comedy My Girl. In 2011, he starred in the SBS romantic drama Scent of a Woman, opposite Kim Sun-ah. His performance in the series won him a Top Excellence Award at the SBS Drama Awards. In 2012, he received the Best Newcomer trophy at the SBS Entertainment Awards for his hosting stint in Strong Heart. In 2014, he reunited with his My Girl leading lady Lee Da-hae in the MBC revenge drama Hotel King, in which he was nominated for two Top Excellence Awards. In 2016, he was cast as a grim reaper in the top-rating and award-winning tvN fantasy series The Lonely Shining Goblin. In 2020, he played the titular character in the well-loved tvN drama Tale of the Nine Tailed.
Lee Dong-wook began his mandatory military service in August 2009. He was discharged in June 2011. He briefly dated singer and actress Suzy. They went public with their relationship in March 2018 but broke up four months later.