John Clark was born in Brooklyn and grew up in Rochester, New York. His father was William H. Clark, a professor of German and dean of education at the University of Rochester, and his mother was Margaret Garmey. He and his four brothers graduated from Brighton High School in Rochester. In 1966 he received a B.A. in Spanish from the University of Rochester, where he also studied horn with Verne Reynolds at the Eastman School of Music. From 1967 until 1971 he played in the United States Coast Guard Band. On 13 September 1967 he married Nancy Puls; they have two children. Clark received an M.M. degree (with honors) from the New England Conservatory of Music in 1973. He studied composition and improvisation with Jaki Byard, Ran Blake, and George Russell; and horn with James Stagliano, Thomas Newell, and Paul Ingraham. In 1991 he received a patent for the "hornette," an instrument with the same range as a French Horn but with a forward facing bell for greater projection. He taught at the State University of New York at Purchase from 2001 until 2008.
As one of only a handful of horn players proficient in non-classical genres, Clark has performed or recorded with a wide variety of musicians. These include Glen Velez, Jerome Harris, Anthony Jackson, Linda Ronstadt, B. B. King, Oliver Lake, Ornette Coleman, McCoy Tyner, Sting, Lew Soloff, David Taylor, Joni Mitchell, Akiko Yano, Leroy Jenkins, Gerry Mulligan, Isaac Hayes, Mike Richmond, Howard Johnson, Carla Bley, Grachan Moncur, Ashford and Simpson, the Brooklyn Philharmonic, Pat Metheny, Frank Sinatra, Dave Grusin, John Scofield, Spyro Gyra, Diana Ross, Carly Simon, LL Cool J, Gil Evans and the Gil Evans Orchestra, Joe Lovano, Jaco Pastorius, Paquito D'Rivera, Jim Hall, Rachel Z, Jimmy Heath, Johnny Griffin, Toots Thielemans, John Faddis, Gary Bartz, Billy Joel, the Fugees, the Trans-Siberian Orchestra, the Turtle Island String Quartet, the Lincoln Center Jazz Orchestra, Speculum Musicae, the Aspen Wind Quintet, and the Paul Winter Consort. He has performed as a studio musician for many films, including Mission to Mars, Fargo, and Pocahontas.
Clark plays the Conn-Selmer 12D and 8D French Horns and uses the AMT (Applied Microphone Technology) microphone systems.