Massine studied acting and dancing at the Imperial School in Moscow and had almost decided to become an actor when Sergey Diaghilev (Diaghilev, Sergey Pavlovich), seeking a replacement for Vaslav Nijinsky, invited Massine to join his company. After a few months of study under Italian dancer and teacher Enrico Cecchetti (Cecchetti, Enrico), Massine made his Paris debut in La Légende de Joseph in 1914 and received favourable comment on his dramatic dance ability and commanding stage personality. Diaghilev supervised his artistic education, taking him to museums and concerts and introducing him to such people as the Russian painter Mikhail Larionov, the conductor Ernest Ansermet, and the composer Igor Stravinsky, all of whom influenced Massine's approach to dance. Diaghilev also encouraged his choreographic talent. Massine's first work as a choreographer, Le Soleil de nuit, was produced in 1915 and was eventually followed by such masterpieces as La Boutique fantasque (1919), Le Tricorne (1919; The Three-Cornered Hat), Le Beau Danube (1924), and Gaîté Parisienne (1938). Massine extended Michel Fokine's choreographic reforms by enriching and clarifying narration and characterizations. His ballets incorporated both folk dance and the demi-caractère dance, a style that uses classical technique to perform character dance. He added variety and complexity by including synchronized yet individual or small-group dance patterns within the corps de ballet.

From 1932 until 1938 Massine was principal dancer and choreographer of Colonel de Basil's Ballet Russe de Monte Carlo. In 1933 he created his first symphonic ballet, Les Présages, using Pyotr Ilyich Tchaikovsky's Fifth Symphony. Although dancers such as Isadora Duncan had previously used symphonic music, Massine's choreography more completely paralleled the structure of the music. The symbolic characterizations of Les Présages were innovative because they relied on dance itself rather than costuming or props to convey their identity. Choreartium, first performed in London (1933) and danced to Johannes Brahms's Fourth Symphony, created even greater controversy; its second movement was close to modern dance in movement style. Critics declared it was both blasphemous and redundant to add dance to these musical masterpieces. With their eventual acceptance, Massine's symphonic ballets effected a choreographic revolution and in turn led to reforms in costuming and sets. Rouge et noir (1939), set to Dmitry Shostakovich's First Symphony, had scenery and costumes by Henri Matisse. Nobilissima Visione, St. Francis (1938) had libretto and music by Paul Hindemith and decor by Pavel Tchelichew. Surrealist painter Salvador Dalí designed three major experimental ballets. Because of disagreements with de Basil, Massine resigned and formed his new Ballet Russe de Monte Carlo, which he headed until 1942. Later he appeared with the Ballet Theatre and the Royal Ballet. In 1966 he joined the newly formed Ballet de Monte Carlo as choreographer and artistic director. He also choreographed and danced in such films as The Red Shoes (1948) and Tales of Hoffmann (1951). Massine's publications include My Life in Ballet (1968) and Massine on Choreography (1976).