With frequent collaborator Lennon Parham, she co-created and co-starred in NBC's Best Friends Forever and USA Network's Playing House.
St. Clair has gained notice for her frequent guest appearances (often alongside performing partner Lennon Parham) on podcasts such as Comedy Bang!
St. Clair has played recurring roles on television shows such as Veep, Weeds, The McCarthys, Marry Me, American Housewife (as protagonist Katie's rival Chloe Brown Mueller), Worst Week and United States of Tara.
St. Clair had a recurring role on the Netflix comedy series Space Force as structural engineer and civil contractor Kelly King.
In 2024, St. Clair and Casey Wilson teamed up to write and narrate the audiobook The Art of Small Talk, which includes interviews with Amy Poehler, Colin Quinn, Malcolm Gladwell, Tony Hale, and June Diane Raphael, among others.