Lee Sang-hee debuted as an actress in the 2010 short horror film Attention. In 2012, she starred in another short film titled Choongshim, Soso, which earned her the Special Jury Prize for Acting at the 2013 Mise-en-scène Short Film Festival. She then took home the Independent Star Award at the 2013 Seoul Independent Film Festival for the short film Children. In 2014, she became part of the drama film End of Winter, which won her Best Actress at the 5th Sakhalin International Film Festival in Russia. In 2016, she acted alongside Ryu Sun-young in the romantic lesbian film Our Love Story, which gave her several Best New Actress trophies, including one from the 53rd Baeksang Arts Awards. In 2017, she joined the main cast of the MBC series 20th Century Boy and Girl, which scored her a Best New Actress nomination at the MBC Drama Awards. In 2019, she was nominated for Best Actress at the 6th Wildflower Film Awards for Jamsil. In 2022, she had appearances in All of Us Are Dead and Juvenile Justice, which were both released on Netflix.

Lee Sang-hee worked as a nurse prior to her foray into acting.