He was born in Venice in Italy and studied composition with Karlheinz Stockhausen as well as studying medicine. He began to make a name for himself as a composer of serial works before gaining fame as a conductor. He was appointed principal conductor of the Philharmonia in 1984 and of the Staatskapelle Dresden in 1992, but is best known for his intense and sometimes controversial interpretations of opera, especially works by Italian composers and Richard Strauss.
Sinopoli died while conducting Giuseppe Verdi's Aïda at the Deutsch Oper in Berlin.