Meyerhold became a student in 1896 at the Moscow Philharmonic Dramatic School under the guidance of Vladimir Nemirovich-Danchenko, cofounder of the Moscow Art Theatre. Two years later, Meyerhold joined the Moscow Art Theatre and there began to formulate his avant-garde theories of symbolic, or “conditional,” theatre. In 1906 he became chief producer at the theatre of Vera Komissarzhevskaya, a distinguished actress of the time, and staged a number of Symbolist plays that employed his radical ideas of nonrepresentational theatre. For his presentation of Henrik Ibsen's Hedda Gabler in 1906, Meyerhold rebelled against the stylized naturalism popularized by Konstantin Stanislavsky's art theatre and instead directed his actors to behave in puppetlike, mechanistic ways. This production marked the beginning of an innovative theatre in Russia that became known as biomechanics (q.v.). Meyerhold's unorthodox approach to the theatre led him to break with Komissarzhevskaya in 1908. Thereafter, drawing upon the conventions of commedia dell'arte and Oriental theatre, he went on to stage productions in Petrograd (St. Petersburg). During 1920–35 Meyerhold achieved his greatest artistic success as a director, beginning with Fernand Crommelynck's Le Cocu magnifique (1920; The Magnificent Cuckold) and ending with his controversial production in 1935 of Aleksandr Pushkin's story “Pikovaya Dama” (“The Queen of Spades”).

Although he embraced the Russian Revolution of 1917, his fiercely individualistic temperament and artistic eccentricity brought reproach and condemnation from Soviet critics. He was accused of mysticism and neglect of Socialist Realism. Meyerhold refused to submit to the constraints of artistic uniformity and defended the artist's right to experiment. In 1939 he was arrested and imprisoned. Weeks later, his actress-wife, Zinaida Raikh, was found brutally murdered in their apartment. Nothing more was heard of him in the West until 1958, when his death in 1942 was announced in the Great Soviet Encyclopaedia; in a later edition the date was changed to 1940.