Fokine was born in Saint Petersburg, as son of a prosperous, middle class merchant and at the age of 9, he was accepted into the Saint Petersburg Imperial Ballet School (Vaganova Ballet Academy). In 1898, on his 18th birthday, he debuted on the stage of the Imperial Mariinsky Theatre in Paquita, with the Imperial Russian Ballet (now the Mariinsky Ballet). In 1902, he became a teacher of the ballet school. Among his students were Desha Delteil and Bronislava Nijinska.

Fokine aspired to move beyond stereotypical ballet traditions. Virtuoso ballet techniques to him were not an end in themselves, but a means of expression. He presented his reformist ideas to the management of the Imperial theatre, but did not win their support.

Some of his early works include the ballet Acis and Galatea (1905) and The Dying Swan (1907), which was a solo dance for Anna Pavlova, choreographed to the music of Le Cygne.

In 1909, Sergei Diaghilev invited Fokine to become the choreographer of his Ballets Russes in Paris. However, Fokine broke off the collaboration in 1912, jealous of Diaghilev's close association with Vaslav Nijinsky.

The Paris premiere of the opera The Golden Cockerel in 1914 was an Opera - Ballet, with Fokine.

He moved to Sweden with his family in 1918 and later established his home in New York City, where he founded a ballet school and continued to appear with his wife, Vera Fokina. He became a United States citizen in 1932.

Fokine staged more than 70 ballets in Europe and the United States. His best known works were Chopiniana (later revised as Les Sylphides), Le Carnaval and Le Pavillon d'Armide. Among his works for the Ballets Russes were The Firebird, Petrushka, Le Spectre de la Rose and Daphnis et Chloé. Also, for the Ballets Russes, he created a ballet out of Rimsky - Korsakov's Scheherazade. His pieces are still performed by the leading ballet troupes of the world, the Mariinsky Ballet having performed a retrospective of his works at London's Covent Garden in late July 2011.

Fokine died in New York on 22 August 1942.