Smith was born in Lemay, Missouri, outside St. Louis. She graduated from the University of Missouri–St. Louis in 1972 with a degree in elementary education. In the 1970s and 1980s, she worked as a dancer, a cheerleader for the old St. Louis football Cardinals, and a burlesque performer ("No stripping, but I did wear feathers," says Smith). She was forced to quit dancing after suffering a knee injury. Smith later worked in Hollywood as an actress and in casting; she was working as a casting associate on The Office when she was offered the role of Phyllis, a character created specifically for her—a sassy woman who tends to disagree with the pompous office manager Michael Scott. Smith received Screen Actors Guild Awards in 2006 and 2007 for her performance in The Office, in the category "Outstanding Performance by an Ensemble in a Comedy Series".
On June 24, 2008, Smith appeared with the cast of The Office on Celebrity Family Feud.
- Alvin and the Chipmunks: Chipwrecked (2011) as Flight Attendant.
- Bad Teacher (2011) as Lynn
- Butter (2011) as Nancy
- The Office: The Outburst (TV series) (2008) as Phyllis
- I Want Someone to Eat Cheese With (2006) as OA Lady - Marsha
- The Office: The Accountants (TV series) (2006) as Phyllis
- The 40-Year-Old Virgin (2005) as Andy's Mother
- Arrested Development (TV series) (2005) as Carla
- The Office (TV series) (2005-2013) as Phyllis Lapin
^ Tracy, Linda (Fall 2008). "It's never just another day at the office for UM-St. Louis alumna Phyllis Smith". UM St. Louis (St. Louis, MO: University of Missouri-St. Louis): 14–15. OCLC 19214058. http://www.umsl.edu/services/creative/pubs/magazine/index.htm.