From 1935 to 1937 she edited the periodical, Axis, devoted to abstract art. In 1937 she married the artist John Piper, with whom she lived in rural surroundings at Fawley Bottom near Henley-on-Thames for much of her life.
Between 1954 and 1973 she collaborated with the composer Benjamin Britten on several of his operas, and between 1977 and 1981 with composer Alun Hoddinott on most of his operatic works. She was a friend of the poet John Betjeman, who wrote several poems addressing her, such as "Myfanwy" and "Myfanwy at Oxford".
John and Myfanwy Piper had two sons and two daughters. Her elder son, painter Edward Piper, predeceased her.