Lee Hee-joon began his acting career through various theater productions and short films. In 2010, he played small roles in the movies The Unjust and The Yellow Sea. He also had appearances in several episodes of KBS Drama Special in 2010 and 2011. His career breakthrough came in 2012 when he joined the KBS2 family drama You Who Rolled In Unexpectedly. His performance in the series won him numerous acting citations, including Best New Actor at the 49th Baeksang Arts Awards. In 2013, he became part of the main cast of the KBS2 series God of the Workplace, which earned him a Best Supporting Actor nomination at the KBS Drama Awards. In 2016, he was nominated for an Excellence Award at the SBS Drama Awards for Legend of the Blue Sea. In 2017, he received a Best Supporting Actor nomination at the 4th Wildflower Film Awards for the melodrama film Worst Woman. In 2020, he starred alongside Lee Byung-heon in the political drama film The Man Standing Next, which gave him the Best Supporting Actor trophy at the 29th Buil Film Awards. In 2021, he scored a Baeksang Best Supporting Actor nomination for the tvN thriller Mouse.

Lee Hee-joon married model Lee Hye-jung in April 2016. He studied chemical engineering at Yeungnam University and theater at Korea National University of Arts.