Producer Kevin McCollum had previously spoken to The New York Times in 2013 about the 1993 movie's musical prospects, noting that the plot was "tailored for Broadway audiences".

[3] On May 16 and 17, 2019, the musical held a reading with a cast including Rob McClure, Kate Baldwin, Mario Cantone, and Jake Ryan Flynn.

Montalvo performed in the Seattle tryout and the three pre-COVID Broadway previews, but died suddenly in October 2020.

Mrs. Doubtfire began Broadway previews on March 9, 2020, at the Stephen Sondheim Theatre, with a planned opening night the following month.

[13] On November 5, 2021, it was announced that the musical will make its UK premiere at the Manchester Opera House the following year, opening on 2 September, and running until 1 October.

The production stars Gabriel Vick as the title role, alongside Laura Tebbutt as Miranda; Carla Dixon Hernandez as Lydia; Samuel Edwards as Stuart; and Cameron Blakely and Marcus Collins as Frank and Andre.

[19] In July 2023, it was announced that Rob McClure would reprise his Tony Award-nominated role as Daniel Hillard/Mrs.Doubtfire for the national tour.

The Broadway production received mixed reviews, with praise for the cast, namely McClure, Scarpaci, Oscar, and Bartlett.