DeGaetani was born in Massillon, Ohio. Educated at The Juilliard School with Sergius Kagen, she was best known for her wide range, precise pitch, clear tone, and command of extended techniques that made her voice perfectly suited to the demanding style of modern and avant-garde vocal composition. Her recording of Schoenberg's song cyclePierrot lunaire is one of the classic recordings of the piece. (Due to its use of atonality, wide range, and virtuoso techniques such as sprechstimme, all while requiring a lyrical sensibility, it is exceptionally difficult to sing.) Her collaboration with George Crumb was also a fruitful one; she premiered his song cycle Ancient Voices of Children, and many of his other works were written for her. Uncommonly for a singer of her caliber (though her voice was not as powerful as most), DeGaetani rarely appeared in opera, instead concentrating on solo recital work in the art song literature.
Her talent at foreign languages also made her an accomplished interpreter of lieder; she sang and recorded works by composers such as Hugo Wolf, Hector Berlioz, and Gustav Mahler and was noted for her intelligence and skillful analytical interpretation. Her interpretive skills also lent themselves to songs in her native tongue of English, such as Aaron Copland's 12 Poems of Emily Dickinson, and the songs of Charles Ives. On the other end of the spectrum, DeGaetani was also a noted performer of the medieval and Renaissance repertoire.