Daniel Hillard is a freelance voice actor in San Francisco. Though a devoted father to his children Lydia, Chris, and Natalie, his wife Miranda considers him unreliable. One day, Daniel quits his job and returns home to throw a lavish birthday party for Chris despite Miranda's objections, creating a situation with their neighbors. Miranda files for divorce, and the judge gives sole custody of the children to her, but tells Daniel if he can find a steady job and a suitable residence within three months, he will agree to share joint custody.
Daniel works to rebuild his life, getting a manager job at a local television station, and learns that Miranda is seeking a housekeeper to watch over the children. He secretly alters her classified ad form to keep other interested people away, and then uses his voice acting skills to call Miranda about the job, making them all undesirable applicants. He then calls Miranda as a Scottish-accented nanny, whom he calls Mrs. Euphegenia Doubtfire, with strong credentials. Miranda is impressed and invites her for an interview. Daniel gets help from his brother Frank, a makeup artist, and his partner Jack to create a Mrs. Doubtfire persona, including a prosthetic mask to make him appear as an older woman.
Miranda hires Mrs. Doubtfire after the impressive interview. The children initially struggle with Mrs. Doubtfire's ways, but soon come around and thrive, and further, Miranda learns to become closer with her children. Daniel, as Mrs. Doubtfire, learns several household skills as part of the role, further improving himself. However, this has created another barrier for Daniel to see his children, as Miranda has put more trust into Mrs. Doubtfire than him, and she could never dismiss her. One day, Lydia and Chris discover Daniel's ploy, and while thrilled to have their father back, agree to keep his secret from Miranda and Natalie, because Miranda would put Daniel in jail and Natalie is 5 years old and would tell Miranda.
While working at the station, Daniel is seen by the station's CEO Jonathan Lundy playing with toy dinosaurs on the set of a cancelled children's show. Impressed by his voice acting and imagination, Lundy asks Daniel to join him for a dinner at Bridge's Restaurant to discuss giving him his own children's show to host. Daniel discovers this is to be on the same night and time as a planned birthday dinner for Miranda by her new boyfriend Stu Dunmire at the same restaurant, which Mrs. Doubtfire has been invited to. Unable to change either appointment, Daniel decides to try to rotate in and out of the Mrs. Doubtfire outfit to attend both events.
As the dinners progress, Daniel gets drunk and starts making mistakes after changing in and out of costume, which he quickly recovers. Stu starts choking on his dinner, and Daniel, in the Mrs. Doubtfire outfit, gives him theHeimlich maneuver. The action causes the prosthetic mask to rip, revealing his identity, and upsetting Miranda.
At their next custody hearing, the judge grants Miranda full custody of the children despite Daniel's ability to secure a job and home. Without Mrs. Doubtfire, Miranda and her children become depressed, recognizing how much Mrs. Doubtfire improved their lives. They are surprised when the local station starts a new children's show, Euphegenia's House, which Daniel, in the Mrs. Doubtfire outfit, hosts. The show becomes a hit and starts airing across the country.
Miranda visits Daniel after one taping and admits they were happier when he was involved, and agrees to contest the custody rights. Soon after, Miranda is able to hire Daniel as the children's new babysitter, able to see the children every day after school—essentially what he was able to do as Mrs. Doubtfire. As Daniel takes the children out, Miranda watches a Euphegenia's House episode where Mrs. Doubtfire answers a letter from a young girl whose parents have separated, saying no matter what arrangements families have, love will prevail.
- Robin Williams as Daniel Hillard / Euphegenia Doubtfire
- Sally Field as Miranda Hillard
- Pierce Brosnan as Stuart "Stu" Dunmeyer
- Harvey Fierstein as Frank Hillard
- Polly Holliday as Gloria Cheney
- Lisa Jakub as Lydia "Lydie" Hillard
- Matthew Lawrence as Christopher "Chris" Hillard
- Mara Wilson as Natalie "Nattie" Hillard
- Robert Prosky as Jonathan Lundy
- Anne Haney as Mrs. Sellner
- Scott Capurro as Jack
- Sydney Walker as Bus Driver
- Martin Mull as Justin Gregory
- Terence McGovern as ADR Director Lou
- William Newman as Mr. Sprinkles