For several years, Rachel Dratch was a member of the cast of the Second City comedy troupe.  She performed alongside future SNL head writers Adam McKay and Tina Fey, as well as future 30 Rock castmate Scott Adsit.

Dratch's first sketch on SNL was "Wicked" performed in Second City's Paradigm Lost. Along with acting, Dratch also played the cello onstage. The theater also hosted the first incarnation of Dratch & Fey, her critically praised two-woman show with Tina Fey. Later, the show was performed at the Upright Citizens Brigade Theatre in New York, where it was dubbed "the funniest thing to be found on any New York comedy stage" by Time Out New York.

Dratch joined SNL in 1999 as a featured player and became a repertory player in 2001 and imitated many people, both real and fictional, including Calista Flockhart, Nicole Richie, Barbara Walters, Jane Eyre, Jenny Jones, Harry Potter, Hilary Duff, and the recurring characters Sheldon Green, Denise "Zazu" McDonough, and Debbie Downer.

Dratch was best known for her Debbie Downer character in the 2004 broadcast of Saturday Night Live. Dratch portrayed a woman who persistently makes comments deemed inappropriate and depressing.