In 1912–14, he designed sets for S. Diagilev's Ballet Troupe productions and for ballets performed on the foreign tours of such leading dancers as A. Pavlova, V. Nijinsky, and V. Fokin. Anisfeld's designs for the sets and costumes of the ballet Islamey composed by M. Balakirev (Mariinsky Theater, St. Petersburg, 1912) brought him well-deserved recognition. In 1915, Anisfeld joined the Jewish Society for the Encouragement of the Arts and participated in its exhibits in Petrograd and Moscow (1916, 1917).

In 1918, Anisfeld and his family settled in New York. His one-man show at the Brooklyn Museum in the same year brought him fame and success in America. In the 1920s, he continued working as a stage designer and created sets for several productions at the Metropolitan Opera. He collaborated with Jewish cultural organizations and associations, lectured at the Educational Alliance Art School, and published prints of his works in the American Yiddish press. In 1924 and 1926, he had one man shows in New York.

In 1928, Anisfeld moved to Chicago and exhibited his works at another one-man show at the Art Institute. In the early 1930s, Anisfeld all but ceased working for theater and focused mainly on painting. He also taught at the Chicago Art Institute until 1958. His later works feature a wide variety of themes and artistic techniques, from realistic landscapes to symbolic paintings executed in the expressionist manner. Big retrospectives of Anisfeld's works were held in Pittsburgh (1946), New York (1956), Chicago (1958), and Washington (1971).