Born in Massachusetts in 1938, Rzewski took private music lessons with Charles Mackey as a child. He studied music at Harvard University, graduating in 1958, and earned an MA from Princeton where he studied composition with Milton Babbitt, and the music of Richard Wagner with Oliver Strunk. In 1960, Rzewski travelled to Florence on a Fullbright scholarship to study with Luigi Dallapiccola for one year. In Europe Rzewski won acclaim as a performance pianist, particularly of new music. He was involved in the premiere of monumental works such as Stockhausen's Klavierstück X (1962). Along with Alvin Curran and Richard Teitelbaum he founded the famous ensemble Musica Electronica Viva (MEV) in Rome in the mid-60s, which became known for its pioneering work with live electronics and improvisation.

In the 70s he began making politically informed works. The best-known pieces of this period are “The People United Will Never Be Defeated!”, a 50-minute set of piano variations, and “Attica”, which includes the recitation of a prison letter. Rzewski has been professor of composition at the Royal Conservatory of Liège, Belgium, since the late 70s.