Yi began by performing in Bloomington, California. After high school, she has performed shows in Los Angeles at The Steve Allen Theater, and The Upright Citizens Brigade Theatre. In 2005 and 2006, she performed in the New York Comedy Festival, and in 2007 HBO's U.S. Comedy Arts Festival in Aspen, Colorado. Yi's film debut was in Judd Apatow's 2007 film, Knocked Up. In 2008, Yi performed as part of the Apatow for Destruction Live comedy show at Montreal's Just For Laughs Festival.
Yi and Paul Rust formed the band The Glass Beef. The duo share one electric guitar and both sing lead vocals. In 2006, they released their debut album, The Farewell Album, produced by John Spiker, Bassist of Tenacious D.
Yi was chosen as one of Venus Zine's "25 under 25" women for 2009.
Yi has been involved with Oxfam America since 2010, working to raise awareness about poverty and hunger around the world. Yi started the non-profit Caring is Cool in 2011, and hosted a benefit show to raise money for the organization.
From October 2011 to May 2012, Yi starred in Fox's series House as Dr. Chi Park, a young Doctor with anger-management issues.
