Oh Yeon-seo debuted in the entertainment industry in 2002 as a member of the short-lived South Korean girl group LUV. She then turned to acting and landed her first role in the 2003 KBS2 series Sharp. In 2009, she appeared in the horror film Whispering Corridors 5: A Blood Pledge. Her career breakthrough came in 2012 when she joined the cast of the KBS2 family drama You Who Rolled In Unexpectedly, which won her Best New Actress at the KBS Drama Awards. In 2013, she starred in the MBC daily series Oh Ja-ryong Is Coming, which scored her another Best New Actress trophy at the MBC Drama Awards. In 2014, she led MBC’s Jang Bori Is Here, which earned her a Top Excellence Award at the MBC Drama Awards. In 2016, she took home an Excellence Award at the SBS Drama Awards for her work in Come Back, Ajusshi. In 2017, she was nominated for a Top Excellence Award at the SBS Drama Awards for the rom-com sageuk My Sassy Girl, which was based on the hit 2001 movie of the same name. Also in 2017, she was cast as the female lead in the tvN fantasy series Hwayugi, opposite Lee Seung-gi.
Oh Yeon-seo attended Dongguk University’s theater and film department. She briefly dated actor Kim Bum.