Piston was born in Rockland, Maine. His father's father, a sailor named Antonio Pistone, changed his name to Anthony Piston when he came to America from Genoa, Italy. In 1905, Walter Piston Sr. and his family moved to Boston. Walter Jr. trained as an engineer at the Mechanical Arts High School in Boston, but he was artistically inclined and upon graduating from there in 1912, proceeded to the Massachusetts Normal Arts School, majoring in painting, also studying architectural drawing and American history. There he met Annabel Nason, and married her at a Unitarian church.

With his brother Edward, Walter Piston Jr. took piano lessons from Harris Shaw (who was Virgil Thomson's organ teacher). During the 1910s Walter Piston made a living playing piano and violin in dance bands, and later on in the decade played violin in orchestras led by Georges Longy. With help from Shaw, Walter Piston was admitted to Harvard in 1920, where he studied counterpoint with Archibald Davison, canon and fugue with Clifford Heilman, advanced harmony with Edward Ballantine, composition and music history with Edward Burlingame Hill. Piston often worked as an assistant to the various music professors there, and conducted the student orchestra.

At about that time Piston joined the U.S. Navy as a musician and learned to play more instruments. The composer himself stated, however, that, when "it became obvious that everybody had to go into the service, I wanted to go in as a musician".

Upon graduating summa cum laude from Harvard, Piston was awarded a John Knowles Paine Traveling Fellowship. He chose to go to Paris, living there from 1924 to 1926. At the Ecole Nationale de Musique in Paris, Piston studied composition and counterpoint with Nadia Boulanger, composition with Paul Dukas and violin with George Enescu. His Three Pieces for Flute, Clarinet and Bassoon of 1925 was his first published score.

He taught at Harvard from 1926 until retiring in 1960. His students include Samuel Adler, Leroy Anderson, Arthur Berger, Leonard Bernstein, Gordon Binkerd, Elliott Carter, John Davison, Irving Fine, John Harbison, Karl Kohn, Ellis B. Kohs, Gail Kubik, Billy Jim Layton, Noël Lee, Robert Middleton, Robert Moevs, Conlon Nancarrow, William P. Perry, Daniel Pinkham, Frederic Rzewski, Allen Sapp, Harold Shapero, and Claudio Spies.

In 1936, the Columbia Broadcasting System commissioned six American composers (Aaron Copland, Louis Gruenberg, Howard Hanson, Roy Harris, William Grant Still and Piston) to write works for CBS radio stations to broadcast. The following year Piston wrote his Symphony No. 1, and conducted its premiere with the Boston Symphony Orchestra on April 8, 1938.

Piston's only dance work, The Incredible Flutist, was written for the Boston Pops Orchestra, which premiered it with Arthur Fiedler conducting on May 30, 1938. The dancers were Hans Weiner and his company. Soon after, Piston arranged a concert suite including "a selection of the best parts of the ballet." This version was premiered by Fritz Reiner and the Pittsburgh Symphony Orchestra on November 22, 1940. Leonard Slatkin and the Saint Louis Symphony Orchestra included the suite in a 1991 RCA Victor CD recording that also featured Piston's Three New England Sketches and Symphony No. 6.

Piston studied the twelve-tone technique of Arnold Schoenberg and wrote works using aspects of it as early as the Sonata for Flute and Piano (1930) and the First Symphony (1937). His first fully twelve-tone work was the Chromatic Study on the Name of Bach for organ (1940), which nonetheless retains a vague feeling of key. Although he employed twelve-tone elements sporadically throughout his career, these become much more pervasive in the Eighth Symphony (1965) and many of the works following it: the Variations for Cello and Orchestra (1966), Clarinet Concerto (1967), Ricercare for Orchestra, Fantasy for Violin and Orchestra (1970), and Flute Concerto (1971).

In 1943, the Alice M. Ditson fund of Columbia University commissioned Piston's Symphony No. 2, which was premiered by the National Symphony Orchestra on March 5, 1944 and was awarded a prize by the New York Music Critics' Circle. His next symphony, the Third, earned a Pulitzer Prize, as did his Symphony No. 7. His Viola Concerto and String Quartet No. 5 also later received Critics' Circle awards.

Piston wrote four books on the technical aspects of music theory which are considered to be classics in their respective fields: Principles of Harmonic Analysis, Counterpoint, Orchestration and Harmony. The last of these went through four editions in the author's lifetime, was translated into several languages, and (with changes and additions by Mark DeVoto) is still widely used by teachers and students of harmony.

Ballet

• The Incredible Flutist (1938)

Orchestral

• Symphonies
• Symphony No. 1 (1937)
• Symphony No. 2 (1943)
• Symphony No. 3 (1946—47) (commissioned by the Koussevitzky Foundation)
• Symphony No. 4 (1950) (composed for the 100th anniversary of the University of Minnesota)
• Symphony No. 5 (1954)
• Symphony No. 6 (1955) (composed for the 75th anniversary of the Boston Symphony Orchestra)
• Symphony No. 7 (1960)
• Symphony No. 8 (1965)

• Suite for Orchestra (1929)
• Concerto for Orchestra (1934)
• Suite from The Incredible Flutist

(The Suite from "The Incredible Flutist" has been transcribed for symphonic wind ensemble by MSgt Donald Patterson and recorded by Col. Michael Colburn with "The President's Own" United States Marine Band.)

• Sinfonietta (1941)
• Suite No. 2 for Orchestra (1948)
• Serenata for Orchestra (1957)
• Three New England Sketches (1959)
• Ricercare for Orchestra (1967)

Band

• Tunbridge Fair, for symphonic band (1950) (Commissioned by the American Bandmasters Association)[1]

Concertante

• Piano
• Piano Concertino (1937)
• Concerto for Two Pianos and Orchestra (1958)
• Violin
• Violin Concerto No. 1 (1939)
• Violin Concerto No. 2 (1960)
• Fantasia for Violin and Orchestra (1970)
• Prelude and Allegro for Organ and Strings (1943)
• Fantasy for English Horn, Harp, and Strings (1954)
• Viola Concerto (1957)
• Capriccio for Harp and String Orchestra (1963)
• Variations for Cello and Orchestra (1966)
• Concerto for Clarinet and Orchestra (1967)
• Concerto for Flute and Orchestra (1971)
• Concerto for String Quartet, Wind Instruments and Percussion (1976)

Chamber/Instrumental

• String quartets
• String Quartet No. 1 (1933)
• String Quartet No. 2 (1935)
• String Quartet No. 3 (1947)
• String Quartet No. 4 (1951)
• String Quartet No. 5 (1962)
• Three Pieces for Flute, Clarinet and Bassoon (1926)
• Flute Sonata (1930)
• Suite for Oboe and Piano (1931)
• Piano Trio No. 1 (1935)
• Violin Sonata (1939)
• Sonatina for Violin and Harpsichord (1945)
• Interlude for Viola and Piano (1942)
• Flute Quintet (1942)
• Partita for Violin, Viola and Organ (1944)
• Divertimento, for nine instruments (1946)
• Duet for Viola and Cello (1949)
• Piano Quintet (1949)
• Wind Quintet (1956)
• Piano Quartet (1964)
• String Sextet (1964)
• Piano Trio No. 2 (1966)
• Duo for Cello and Piano (1972)

Piano

• Piano Sonata (1926)
• Passacaglia (1943)
• Improvisation (1945)

Organ

• Chromatic Study on the Name of BACH (1940)

Choral

• Psalm and Prayer of David (1959)

Books

• Principles of Harmonic Analysis. Boston: E. C. Schirmer, 1933.
• Harmony. New York: W. W. Norton & Company, Inc., 1941. Reprint edition (as U.S. War Dept. Education Manual EM 601), Madison, Wisc.: Published for the United States Armed Forces Institute by W. Norton & Co., 1944. Revised ed, New York: W. W. Norton & Co., 1948. Third ed., 1962. Fourth ed., revised and expanded by Mark DeVoto, 1978. ISBN 0-393-09034-5. 5th edition, revised and expanded by Mark DeVoto ISBN 0-393-95480-3. British editions, London: Victor Gollancz, 1949, rev. ed. 1950 (reprinted 1973), 1959, 3rd ed. 1970, 4th ed. 1982. Spanish translation, as Armonía, rev. y ampliada por Mark DeVoto. Barcelona: Idea Books, 2001. ISBN 8482362240 Chinese version of the 2nd edition, as ??? [He sheng xue], trans. Chenbao Feng and Dunxing Shen. ?? : ??????? : ??????????? [Beijing: Ren min yin yue chu ban she : Xin hua shu dian Beijing fa xing suo fa xing], 1956. Revised, ?? : ??????? [Beijing: Ren min yin yue chu ban she], 1978.
• Counterpoint. New York: W. W. Norton & Company, Inc., 1947.
• Orchestration. New York: Norton, 1955. Russian translation, as '???????????', translation and notes by Constantine Ivanov. Moscow: Soviet Composer, 1990, ISBN 5-85285-014-4.