Mullen began performing on The Muppet Show in its third season, primarily as Gaffer the Backstage Cat. She also voice directed Dog City for Nelvana, worked as a designer for The Muppet Movie, right-handed for Frank Oz on Yoda on The Empire Strikes Back, and was one of the creators of Between the Lions. While reprising Gaffer for several Muppet movies, she also performed Mokey Fraggle and Cotterpin Doozer on Henson's Fraggle Rock. She performed the Gelfling Kira in the movie The Dark Crystal, Allegra on Allegra's Window, and Leona the Lion on Between the Lions.
Mullen, with her husband, former Muppet designer Michael K. Frith, founded "No Strings" along with emergency aid worker Johnie McGlade. The company originally created a film for children in Afghanistan, warning of the dangers of land mines. In the film, "The Story of the Little Carpet Boy," one puppet loses several limbs before he learns to avoid land mines completely. Since the first film, No Strings has gone on to create films for children in need in areas including Africa, Haiti, Madagascar, Sudan, and Syria. In 2016 No Strings was awarded the 2016 Adela Dwyer-St. Thomas of Villanova Peace Award from Villanova University
In 2013, Mullen attended Dragon Con with Karen Prell and Michael K. Frith as part of the 30th Anniversary of Fraggle Rock where Kathryn Mullen performed Mokey Fraggle while Karen Prell performed Red Fraggle.

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