Flanagan officially joined the cast of MADtv in 2005 as a featured performer, for the 10th season, then became a repertory cast member at the beginning of the following season. Her frequent impersonations were of Alex Hooser, Ellen Pompeo, Heidi Klum, Patricia Arquette (as Allison DuBois from Medium), Natalie Maines of the Dixie Chicks, and Miley Cyrus (as herself and as Hannah Montana from the Disney Channel show of the same name).

Crista had a long-standing gag with fellow cast member Bobby Lee, where their behind-the-scenes characters had a love/hate relationship. This relationship can be seen in the "Secret Santa" skit, where Bobby proposes to Crista, to which she replies, "I cannot marry someone I have a restraining order against." This can also be seen in the "Celebrity Triathlon" skit, where Crista slams the door after Bobby asks for her help, and she makes reference to not helping him dig up a dead body, but reluctantly agrees to help him train.