Tairov took up law briefly before settling on a theatrical career. He worked in several companies, including that of the Mobile Theatre of P.P. Gaydeburov. In 1913–14 he managed the shortlived Free Theatre Moscow prior to founding the Kamerny.

In the wake of the Bolshevik Revolution—at a time when the United States had broken off diplomatic relations with the Soviet Union—Tairov brought to Moscow audiences the work of the American playwright Eugene O'Neill, notably The Hairy Ape, All God's Chillun Got Wings, and Desire Under the Elms. Tairov's style was avant garde, particularly with respect to staging. He helped develop the functional “constructivist” setting, a bare, multilevel scaffolding devoid of traditional decorative scenery. His approach to theatre was stylized and antirealistic and was diametrically opposed to that of the followers of actor-director Konstantin Stanislavsky. He attached great importance to the actor's physical attributes; members of his company were rigorously trained in dancing, singing, acrobatics, and rhythmic precision of move ment. His 1934 production of Vsevolod Vishnevsky's The Optimistic Tragedy was regarded as a high point of Socialist Realist theatre. Under pressure from Stalinist authorities, however, Tairov was eventually compelled to work under the guidance of a state theatre committee. His wife, Alisa Koonen, starred in many of his productions.