In 1968 Monk founded the House, a company dedicated to an interdisciplinary approach to performance. In 1978 she founded Meredith Monk & Vocal Ensemble to expand her musical textures and forms. As a pioneer in site-specific performance, she has created such works as Juice: A Theatre Cantata In 3 Installments (1969) and Ascension Variations (2009) for the for the Guggenheim Museum, and American Archeology #1: Roosevelt Island (1994). Monk's award-winning films, including Ellis Island (1981) and her first feature, Book of Days (1988), have been seen throughout the world. Her music can also be heard in films by such directors as Jean-Luc Godard and the Coen Brothers and in the recent HBO series True Detective. In addition to her numerous vocal pieces, music-theater works and operas, Monk has created vital new repertoire for orchestra, chamber ensembles and solo instruments, with commissions from Michael Tilson Thomas/San Francisco Symphony and New World Symphony, Kronos Quartet, Saint Louis Symphony Orchestra and Los Angeles Master Chorale, among others.

Since graduating Sarah Lawrence College in 1964, Monk has received numerous honors including the prestigious MacArthur "genius" award, two Guggenheim fellowships, three "Obies" (including an award for Sustained Achievement), and two "Bessie" awards for Sustained Creative Achievement. She holds honorary Doctor of Arts degrees from Bard College, the University of the Arts, the Juilliard School, the San Francisco Art Institute and the Boston Conservatory. Monk has made more than a dozen recordings, most of which are on the ECM New Series label, including the 2008 Grammy-nominated impermanence and the highly acclaimed Songs of Ascension. She has also been working with the publisher Boosey & Hawkes since 2001.

In October 1999 Monk performed A Vocal Offering for the Dalai Lama as part of the World Festival of Sacred Music in Los Angeles. Her 40th year of performing and creating new music was celebrated in 2005 by a four-hour marathon at Carnegie's Zankel Hall, with additional performances throughout New York City. In February 2012 she was honored with a remix and interpretations cd, Monk Mix, featuring 25 artists from the jazz, pop, DJ and new music worlds. In March 2012 she premiered Realm Variations for six voices and small ensemble, commissioned by the San Francisco Symphony and performed in John Cage's Song Books as part of the Symphony's American Mavericks Festival. Monk's newest music-theater piece, On Behalf of Nature, premiered in January 2013 at UCLA and is currently touring internationally. This fall Meredith Monk will mark her 50th season as a creator and performer. Recognized as one of the most unique and influential artists of her generation, she has been appointed the 2014–15 Richard and Barbara Debs Composer's Chair at Carnegie Hall.