The son of a violinist with the New York Philharmonic, he studied at the Saint Thomas Choir School and became an accomplished horn player and flute player. At age 15 he played horn professionally with the American Ballet Theatre (1943) followed by an appointment as principal hornist with the Cincinnati Symphony Orchestra (1943–5), and then the Metropolitan Opera Orchestra in New York (1945–59). He began his career in jazz by recording as a french horn player with Miles Davis (1949–50).
In 1955 Schuller and jazz pianist John Lewis founded the Modern Jazz Society, which gave its first concert in Town Hall, New York, that same year and later became known as the Jazz and Classical Music Society. While lecturing at Brandeis University in 1957 he coined the term "Third Stream" to describe music that combines classical and jazz techniques. He became an enthusiastic advocate of this style and wrote many works according to its principles, among them Transformation (1957, for jazz ensemble), Concertino (1959, for jazz quartet and orchestra; one of its movements, Progression in Tempo, has sometimes been performed separately), Abstraction (1959, for nine instruments), the opera The Visitation (1966), and Variants on a Theme of Thelonious Monk (1960, for 13 instruments), which was recorded by Ornette Coleman, Eric Dolphy, and Bill Evans. He also orchestrated Scott Joplin's only known surviving opera Treemonisha for the Houston Grand Opera's premier production of this work.
In 1959 Schuller gave up performance to devote himself to composition. He has conducted internationally and studied and recorded jazz with such greats as Dizzy Gillespie and John Lewis among many others. Schuller has written over 160 original compositions. In the 1960s, Schuller was president of New England Conservatory. He created the jazz program at NEC, which today is one of the strongest jazz centers in the world.
Schuller is editor-in-chief of Jazz Masterworks Editions, and co-director of the Smithsonian Jazz Masterworks Orchestra
in Washington, D.C. Another recent effort of preservation was his editing and posthumous premiering at Lincoln Center in 1989 of Charles Mingus' immense final work, Epitaph, subsequently released on Columbia/Sony Records.
His notable students include Irwin Swack. 
Gunther is the father of jazz percussionist George Schuller and bassist Ed Schuller.
Grammy Award for Best Album Notes - Classical:
Grammy Award for Best Chamber Music Performance: