Mischakoff was born in Proskuriv (today Khlmelnytskyi), Ukraine as Mischa Fischberg. In 1921 he escaped from Russia with, among others, his friend and colleague, cellist Gregor Piatigorsky, with whom he had played in the Bolshoi Theatre in Moscow. Mischakoff emigrated to the United States later that year, becoming a naturalized citizen in 1927.
He led the string sections of the St. Petersburg Conservatory Orchestra, St. Petersburg Philharmonic Orchestra, Moscow Bolshoi Theatre, Warsaw Philharmonic Orchestra, then, after his arrival in the United States, the New York Symphony under Walter Damrosch (1920–1927), the Philadelphia Orchestra under Leopold Stokowski (1927–1930), the Chicago Symphony Orchestra under Frederick Stock (1930–1937), the NBC Symphony Orchestra under Arturo Toscanini (1937–1952), the Detroit Symphony Orchestra under Paul Paray (1952–1968), as well as, in retirement, the Baltimore Symphony Orchestra.
Mischa Mischakoff also led the Mischakoff String Quartet in the various cities where he lived, and between 1940 and 1952 he taught at the Juilliard School in New York.
Mischakoff died on February 1, 1981 in Petoskey, Michigan. He owned four Stradivari violins, on which he appeared as soloist and recitalist, as well as a number of other fine violins by old and contemporary makers.
The biography of Mischa Mischakoff does not include his long association as concertmaster of the Chautauqua Symphony at Chautauqua Institution, Chautauqua NY. There, Mischakoff also led the Mischakoff String Quartet which gave weekly recitals during the summer season.