Seo Ji-hye began her acting career in the 2003 SBS series All In. In 2005, she was named Best New Actress at the MBC Drama Awards for her performance in Shin Don. In 2011, she became part of the SBS drama 49 Days, which earned her an Excellence Award nomination at the SBS Drama Awards. The following year, she won an Excellence Award at the KBS Drama Awards for her work in daily series Moon and Stars for You. In 2015, she took home the Best TV Star trophy at the 15th Gwangju International Film Festival for the SBS series Punch. In 2016, she appeared in the SBS workplace romantic comedy Jealousy Incarnate, which scored her a Special Acting Award at the SBS Drama Awards. In 2018, she bagged an Excellence Award at the SBS Drama Awards for the medical drama Heart Surgeons. In 2020, she played a North Korean heiress in the hit tvN series Crash Landing on You, which gave her the Bazaar Icon Award at the 56th Baeksang Arts Awards. In 2021, she was paired with Song Seung-heon in the MBC romance drama Will You Have Dinner With Me.

Seo Ji-hye majored in acting at the Sungkyunkwan University.