After graduating from Wellesley College, the Clarksburg native made her major debut in 1946. She joined the New York City Opera in 1953, singing many roles, including all the main female roles by Mozart. She became known for singing new, modern operas. Over 50 new pieces were written just for her voice. In 1955, she premiered the main role in the famous American opera Susannah by Carlisle Floyd.

Phyllis Curtin made her debut at the Metropolitan Opera in 1961. She gained an international reputation, singing in famous opera houses Milan, Italy, and Vienna, and Austria.

In 1968, she was named West Virginian of the Year In 1976, she was invited to sing at the White House for President Gerald Ford. After retiring from singing in 1984, she taught at Yale University and served as dean of the Boston University School of the Arts until 1991.

She received a Lifetime Achievement Award in 1999 and was inducted into the West Virginia Music Hall of Fame in 2008.