Coming from a theatrical family, she performed her first professional show at the age of three as the Duke of York in Richard III.

(March 18, 1928), Harrison Grey Fiske was 12 years old when he first set eyes on the future Mrs. Fiske—she was but eight, performing in a Shakespearean role.

[3] Leaving a life of domesticity, she returned to the theatre in 1893 as a playwright and director, having written one-act plays such as A Light for St. Agnes, The Rose, and The Eyes of the Heart.

Among her many triumphs on the Broadway stage were: Tess of the d'Urbervilles (1897, revival 1902), Love Finds the Way (1898), Becky Sharp (1899, revivals 1904, 1911), A Doll's House (1902), Hedda Gabler (1903, revival 1904), Leah Kleschna (1904–05), Salvation Nell (1908–09), The High Road (1912–13), Madame Sand (1917–18), a play about George Sand; Mis' Nelly of N'Orleans (1919), Helena's Boys (1924), Ghosts (1927), Ladies of the Jury (1929–30), as well as her self-written plays The Rose (1905), The Eyes of the Heart (1905), A Light from St. Agnes (1906).

She told The New York Times in January 1908: Ibsen is of interest to the actor because properly to understand a role you must study the character from its earliest childhood.

The beautiful verse, the wonderful character drawing of Shakespeare furnish solutions of perplexing problems, but Ibsen is so elusive.

[7][8]Although she was highly praised as an actor, she died poverty-stricken, having fought against a group of producers that organized the Theatrical Trust or Syndicate.

She fought for artistic freedom for 12 years, which caused her to perform in third-class theatres, such as churches and skating rinks.

[9] She fought against the wearing of the plumes of snowy and great egrets on hats, raised awareness of the cruelties of fur trapping, and changed the treatment of cattle on ranges.

[4] She was twice named one of the twelve greatest living American women because of her fight for animal rights and for her outstanding talent.

[3] Mark Twain wrote the story "A Horse's Tale" at her request to combat bullfighting in Spain.

[17] During World War II, the Liberty ship SS Minnie M. Fiske was built in Panama City, Florida, and named in her honor.