The son of a Russian Army captain, Ussachevsky spent his childhood on the desolate, frigid plains of Manchuria, where his ears were inculcated with traditional Slavonic chants as an altar boy in the Russian Orthodox church. By the time he emigrated to the United States at the age of nineteen, he was already a talented pianist with an aptitude for improvisation and a flair for interpretation of the Romantic literature. After obtaining his Ph.D. in composition from the Eastman School of Music in 1939, Ussachevsky gained a professorship at Columbia University, a position he held for 34 years. Some of his notable pupils included Charles Dodge, Robert Moog, Alice Shields, Harvey Sollberger, and Charles Wuorinen.

In October 1952, he and Otto Luening gave their now legendary concert of tape music at the Museum of Modern Art in New York, the first ever of its kind in the United States. A Rockefeller Foundation grant enabled him to found in 1959, along with his teacher and later collaborator Otto Luening, the first American electroacoustic studio, the Columbia-Princeton Electronic Music Center. Ussachevsky authored a highly inventive and emotionally expressive body of works, and his unique contributions to the field of early electronic music should not be underestimated.