Horenstein was born in Kiev. He studied in Vienna with Franz Schreker among others before moving to Berlin and working as an assistant to Wilhelm Furtwangler. During the 1920s he conducted the Vienna Symphony Orchestra and the Berlin Philharmonic Orchestra before moving to the United States of America in the 40s (he eventually became an American citizen). He died in London.
Horenstein is particularly remembered for championing modern music (in 1929 he conducted the premiere of the arrangement for strings of three movements of Alban Berg's Lyric Suite), and for his advocacy of the works of Anton Bruckner and Gustav Mahler at a time when both composers were very unfashionable.