After studying at Miami University in Oxford, Ohio she came to New York City taking lessons from musicians such as Steve Lacy. Together with her husband, percussionist Frank Clayton, she presented Jazz at the Loft in their home in about 1967: Sam Rivers, Cecil McBee, Joanne Brackeen, Dave Liebman, Larry Karush, Pete Yellin, Hal Galper, Jeanne Lee, Bob Moses, Junie Booth, John Gilmore, and Jane Getz were among the featured musicians. Clayton also began to earn her own reputation as an avant-garde singer, developing her personal wordless vocabulary.
Clayton's pioneering vocal explorations placed her at the forefront of the free jazz movement and loft scene in the 1970s, where she counted among the first singers to incorporate poetry and electronics into her improvisations. She performed and recorded with Muhal Richard Abrams, with John Fischer's Interface, and Byron Morris's Unity. For a long time she was a member of the Steve Reich ensemble, performing the compositions of the minimalist composer. She was one of the first singers to record composer John Cage’s vocal music.
Clayton's own performance dates appear under the heading the Jay Clayton Project, while she titles her work with other esteemed vocalists Different Voices. She co-leads a trio, Outskirts, with drummer Jerry Granelli and saxophonist Jane Ira Bloom.
With more than 40 recordings to her credit, Clayton has appeared alongside such formidable artists as Bud Shank, Charlie Haden, Kirk Nurock, Stanley Cowell, Lee Konitz, Julian Priester, George Cables, Gary Bartz, Gary Peacock and Fred Hersch, as well as fellow vocalists Jeanne Lee, Lauren Newton, Urszula Dudziak, and Bobby McFerrin. In 1971, Clayton began leading her own workshops, partly together with Michelle Berne and Jeanne Lee.
From 1981 onwards, Clayton taught at Cornish College of the Arts in Seattle, Washington for 20 years. In addition to that tenure, Clayton taught for several semesters at New York's City College, at several European universities (Graz (Austria), Berlin, Cologne, Munich). She developed the vocal program for the Banff Center (Canada), which she co-taught with fellow vocalist Sheila Jordan. The two are also teaching together at Vermont Jazz Workshop and at Jazz in July (at the University of Massachusetts Amherst). Clayton has brought her masterclasses to the Manhattan School of Music and the Peabody Conservatory. Her book, Sing Your Story: A Practical Guide for Learning and Teaching the Art of Jazz Singing, was published in 2001.
In 1979, Clayton acted as the artistic director for the first ever Women in Jazz Festival (produced by Cobi Narita). She served as a consultant for ABC Cable's Women in Jazz, compiling footage for the series. Clayton received grants from the National Endowment for the Arts, Meet the Composer, and Chamber Music America.
- Clayton, Jay; Jane Ira Bloom; Frank Clayton; Larry Karush; Harvie Swartz (1980). All Out. Anima. (
- Clayton, Jay; Don Lanphere (1988). Jay Clayton & Don Lanphere: TheJazz Alley Tapes. Hep Records.
- Clayton, Jay (1988). Jay Clayton with the String Trio of New York. West Wind Records.
- Clayton, Jay; Stanley Cowell; Gary Peacock (1995). Live at Jazz Alley. ITM Records.
- Clayton, Jay; Jim Knapp (1995). Tito's Acid Trip. ITM Records.
- Clayton, Jay (1997). Circle Dancing. Sunnyside Records.
- Clayton, Jay; Jerry Granelli; George Cables; Anthony Cox; Gary Bartz (2001). Brooklyn 2000. Sunnyside Records.
- Clayton, Jay; Jerry Granelli (2001). Sound Songs. Winter & Winter.
- Clayton, Jay (2002). An American Garden. Solo Winds.
- Clayton, Jay (2002). Beautiful Love. Sunnyside Records.