At age 9, Horowitz entered the Kiev Conservatory after having studied first with his mother, Sofia, herself an accomplished pianist. Among his teachers was conductor, pianist and composer Felix Blumenfeld (1863-1931), who had studied with Rimsky-Korsakov and worked closely with Anton Rubinstein, one of the greatest pianists of the 19th century.

Horowitz made his American debut on January 12, 1928, with conductor Sir Thomas Beecham and the New York Philharmonic, at one of the most memorable concerts at Carnegie Hall. Beecham had been rehearsing Tchaikvosky's First Piano Concerto at very slow tempos. When Horowitz heard an even slower tempo at the time of the performance, he decided to take matters into his own hands and play his own tempo. The result, according to Carnegie Hall archivist Gino Francesconi, "Horowitz played more notes faster than the entire Philharmonic." The audience went wild, and a legend was born. Over 57 years, Horowitz performed at Carnegie Hall 97 times.

While Horowitz was an unrivaled virtuoso and showman, and was widely considered the greatest living interpreter of the Romantic composers, including Rachmaninoff, Liszt, and Schumann, he never felt that he was living up to his full potential. As a result, Horowitz retired four times, from 1936 to 1938, 1953 to 1965, 1969 to 1974, and finally from 1983 to 1985.