Born in Berdichev in what is now Ukraine, Horowitz had piano lessons from an early age, initially from his mother, who was herself a professional pianist. In 1912 he entered the Kiev Conservatory, leaving in 1919, and playing the third piano concerto of Rachmaninov at his graduation. His first solo recital followed in 1920.
His star rapidly rose - he soon began to tour Russia, and in 1926 made his first appearance outside his home country, in Berlin. He later played in Paris, London and New York City, and it was in the United States that he eventually settled in 1940. He became an American citizen in 1944.
In 1932 he played for the first time with the conductor Arturo Toscanini in a performance of Beethoven's Piano Concerto No. 5 (the Emperor concerto). The two went on to appear together many times, both on stage and on record. In 1933, Horowitz married Wanda Toscanani, the conductor's daughter.
Despite receiving rapturous receptions at his recitals, Horowitz became increasingly unsure of his abilities as a pianist. Several times he withdrew from public performances, and it is said that on several occasions, the only thing that stopped him from cancelling recitals at the last moment was the persuasiveness of his wife. After 1970 he gave solo recitals only rarely. He played chamber music in public, however, the presence of another musician on stage apparently helping with his insecurities. He also made several recordings.
In 1986, Horowitz made a return to the Soviet Union to give a series of concerts. In the new atmospere of communication and understanding between the USSR and the USA, they were seen as events of some political, as well as musical, significance.
Horowitz is best known for his performances of the romantic repertoire, with his recordings of Rachmaninov's Piano Concerto No. 3 being particularly highly acclaimed. He was sometimes accused of self indulgence in his performances, but his extravagances were always well received by his audiences. He had an unusual technique, played with very straight fingers. He did much to champion contemporary Russian music, giving the American premieres of Sergei Prokofiev's 6th, 7th and 8th piano sonatas, although his performances of these works are sometimes criticized today.