Following her role as Lily in Thomas and the Magic Railroad (2000), Wilson took a 12-year hiatus from acting to focus on writing.

[16] When Wilson was five, she became interested in acting after watching her older brother Danny appear in television commercials.

[17] Wilson sang "Make 'Em Laugh" at the 67th Academy Awards broadcast on March 27, 1995, with Tim Curry and Kathy Najimy.

[20] A year later, she auditioned for the 1998 remake of Disney's The Parent Trap, but the role was given to Lindsay Lohan after Wilson was deemed too young.

[21] In 1999, she portrayed Willow Johnson in the film for The Wonderful World of Disney titled Balloon Farm.

[25][26] In 2012, Wilson appeared briefly in one episode of the web series Missed Connection in the role of Bitty, and made special appearances on internet review shows for That Guy with the Glasses, including a comedic turn playing an adult Matilda during a review of Matilda by The Nostalgia Chick, Lindsay Ellis.

[40][41][42] Wilson had a recurring role on the podcast Welcome to Night Vale as "The Faceless Old Woman Who Secretly Lives in Your Home", as well as her own storytelling show called What Are You Afraid Of?

[43][44] In 2016, Wilson made a brief return to television in a Mrs. Doubtfire-inspired episode of Broad City, in which she played a waitress where the comical Heimlich scene from the film was re-enacted.

[45][46] That same year, Wilson voiced Jill Pill, a writer/director anthropomorphic spider, in season 3 of BoJack Horseman.

[50][51][52] In May 2024, she reunited with Mrs Doubtfire cast members Lisa Jakub and Matthew Lawrence for a joint podcast appearance.

[55][56] In 2015, Wilson collaborated with Project UROK, a nonprofit organization whose mission is to aid teens with mental illness.

[58] She is a cousin of political commentator and media host Ben Shapiro,[59][60] whom she has disavowed due to his conservative views and her left-wing beliefs;[5] the two have no contact with each other.

[64] In 2014, she was working for the non-profit Publicolor, a New York City-based nonprofit involved in repainting public schools.

Wilson described her disappointment when a reporter called her a "spoiled brat" after she stated that she wanted the day off on her 13th birthday instead of granting interviews.