Lee Yumi made her acting debut in the 2010 action thriller movie The Yellow Sea. In 2017, she acted a supporting role in the MBC series 20th Century Boy and Girl. The following year, she appeared in OCN’s Voice 2 and KBS2’s Dance Sports Girls. In 2020, she played a university student suffering from a factitious disorder called Munchausen syndrome in the MBC fantasy mystery series 365: Repeat the Year. In 2021, she starred in the film Young Adult Matters as a pregnant high school student who runs away from home to get an abortion. The movie won her Best New Actress at the 30th Buil Film Awards and also earned her a Best New Actress nomination at the 42nd Blue Dragon Film Awards. Later that year, she shot to fame after portraying a recurring role in the mega hit Netflix survival drama Squid Game. Her work in the series made her the first Korean to be named Outstanding Guest Actress in a Drama Series at the 2022 Primetime Creative Arts Emmy Awards.

Lee Yumi developed a close friendship with her Squid Game co-star Jung Ho-yeon, who is the same age as her.