For Disney, she played for playing Mary Sanderson in the 1993 Halloween comedy film, Hocus Pocus. She played Sister Mary Patrick in the Touchstone Pictures movie Sister Act in 1992 and in its sequel Sister Act 2: Back in the Habit in 1993. She has also appeared as Mariah in the 2002 Disney Channel Original Movie, The Scream Team. In an episode of The Suite Life of Zack and Cody, she played the principal. Her most recent role in a Disney film was Mary in the 2008 Pixar film, Wall-E. She also voiced Dania in The Legend of Tarzan episode, "Tarzan and the Rift".
She also made a cameo appearance on Muppets Tonight in "The Gary Cahuenga Episode." Najimy played "Estelle, God of Hunger," an employee at the Department of Motor Vehicles, in a "Thor, God of Thunder" sketch. She also played Dr. Femus in the former Magic Kingdom attraction, ExtraTERRORestrial Alien Encounter.