Before breaking into television, Flynn was a member of The Second City improv troupe in 1975. She appeared on stage alongside Shelley Long, George Wendt, Andrea Martin, Catherine O'Hara, and James Belushi.
Her best known film role is as Cousin Catherine in National Lampoon's Vacation (1983), National Lampoon's Christmas Vacation (1989), Vegas Vacation (1997) and National Lampoon's Christmas Vacation 2: Cousin Eddie's Island Adventure (2003). Her other acting roles include First Family (1980), National Lampoon's Class Reunion (1982), Mr. Mom (1983), For Keeps (1988), 18 Again! (1988), Stealing Home (1988), Lonely Hearts (1991), Evolution (2001), Wieners (2008), About Fifty (2011) and Bucky Larson: Born to Be a Star (2011).
Flynn was a regular cast member in The Tim Conway Show, a comedy-variety show that aired on CBS from March 1980 through summer 1981, acting in Sketch comedy in each episode. She then starred in her own sitcom, Maggie, on ABC, but the show was short-lived, airing in October and November 1981 and in April–May 1982 before being cancelled. She appeared in an episode of the classic television show Cheers entitled "Love Thy Neighbor" (Season 4, Episode 8, air date November 21, 1985) in which she played Phyllis Henshaw, Norm & Vera Peterson's next-door neighbor. In fall 1988, she co-starred in the short-lived CBS sitcom Raising Miranda.
In 1995, she was the voice of Maa, a very old Ewe in the hit film, Babe. In 1996–1997, she was a regular cast member in Malcolm & Eddie, playing Kelly, a bar owner and landlord to the main characters, for the program's first season.
From 2001 to 2005 she played the recurring character Sister Helen on the Fox/WB sitcom Grounded for Life. In 2004, she played Coop's mom in Megas XLR.
