Seo Ye-ji debuted as an actress in the 2013 tvN sitcom Potato Star 2013QR3. Her career quickly picked up after she played one of the main leads in MBC’s Records of a Night Watchman, which earned her a Best New Actress nomination at the MBC Drama Awards. That same year, she appeared in tvN’s Superdaddy Yeol and JTBC’s Last. In 2016, she joined the KBS2 dramas Moorim School and Hwarang. In 2017, she starred in the OCN thriller Rescue Me along with Taecyeon, Jo Sung-ha, and Woo Do-hwan. In 2018, she acted alongside Lee Jun-ki in the tvN legal-action drama Lawless Attorney. In 2019, she became part of the crime film By Quantum Physics: A Nightlife Venture, which gave her the Popular Star Award at the 29th Buil Film Awards. In 2020, she was paired with Kim Soo-hyun in the hit tvN series It’s Okay to Not Be Okay, which won her numerous awards including the Baeksang Most Popular Actress trophy.

In 2021, Seo Ye-ji was accused of allegedly manipulating her then-boyfriend Kim Jung-hyun while he was filming his MBC series Time in 2018. She reportedly demanded the actor to decline shooting any romantic scenes in the drama and to act cold toward female co-stars and crew members on the set. Kim Jung-hyun eventually stepped down halfway through the series. Almost a year after the controversy, Seo Ye-ji issues an official apology.