The New York Times has called him a "social conscience, multimedia collaborator, system builder, rhapsodist, historical thinker and multicultural gateway".

[11] In 2014, he was jointly appointed with tenure to Harvard University's departments of music and African American studies as the Franklin D. and Florence Rosenblatt Professor of the Arts.

[12][13] Born in Albany and raised in Fairport, New York (a suburb of Rochester),[14] he is the son of Brahmin Indian Tamil immigrants to the United States.

"[19] While in graduate school he continued to pursue his musical interests, playing in ensembles led by the drummers E. W. Wainwright and Donald Bailey.

In 1995, concurrently with his composing, recording and touring, he left the Berkeley physics department and assembled an interdisciplinary Ph.D. degree program in technology and the arts, focusing on music cognition.

He has collaborated with Amiri Baraka, Teju Cole, Wadada Leo Smith, Arooj Aftab, Steve Coleman, Roscoe Mitchell, Oliver Lake, Henry Threadgill, Reggie Workman, Andrew Cyrille, Amina Claudine Myers, Butch Morris, George E. Lewis, Craig Taborn, Rudresh Mahanthappa, Kassa Overall, Linda May Han Oh, Liberty Ellman, Robert Stewart, Yosvany Terry, Okkyung Lee, Miya Masaoka, Francis Wong, Hafez Modirzadeh, Amir ElSaffar, Matana Roberts, Trichy Sankaran, L. Subramaniam, Zakir Hussain, Aruna Sairam, Pamela Z, Burnt Sugar, Karsh Kale, Mike Ladd, DJ Spooky, dead prez, HPrizm, Das Racist, Himanshu Suri, Will Power, Karole Armitage, the Brentano Quartet, the Imani Winds, the International Contemporary Ensemble, the Parker Quartet, Matt Haimovitz, Claire Chase, Jennifer Koh, Miranda Cuckson, Prashant Bhargava and Haile Gerima.

In 2003, Iyer premiered his first collaboration with the poet-producer-performer Mike Ladd, In What Language?, a song cycle about airports, fear and surveillance before and after 9/11, commissioned by the Asia Society and released in 2004 on Pi Recordings.

His next project with Ladd, Still Life with Commentator, a satirical oratorio about 24-hour news culture in wartime, was co-commissioned by UNC-Chapel Hill and the Brooklyn Academy of Music for its 2006 Next Wave Festival.

[21] In 1996, Iyer began collaborating with the saxophonist Rudresh Mahanthappa, resulting in five albums under Iyer's name (Architextures (1998), Panoptic Modes (2001), Blood Sutra (2003), Reimagining (2005) and Tragicomic (2008)), three under Mahanthappa's name (Black Water, Mother Tongue, Code Book), and a duo album, Raw Materials (2006).

He collaborated with the filmmaker Bill Morrison on the short film and audiovisual installation Release (2009), commissioned by the Eastern State Penitentiary in Philadelphia, Pennsylvania, which is now operated as an historic site.

In 2014, he premiered Time, Place, Action, a piano quintet he performed with the Brentano Quartet, and Bruits, a sextet for Imani Winds and the pianist Cory Smythe, later recorded on their Grammy-nominated 2021 album of the same name.

In 2019, Iyer composed Crisis Modes for strings and percussion, co-commissioned by the Los Angeles Philharmonic, Kölner Philharmonie and Wigmore Hall, Hallucination Party commissioned by Mishka Rushdie Momen and recorded on her album Variations, and Song for Flint for viola solo, commissioned by Miller Theatre at Columbia University and premiered in Iyer's Portrait Concert there on October 24, 2019.

[31] In 2014, Iyer joined the senior faculty in the Department of Music at Harvard University as the Franklin D. and Florence Rosenblatt Professor of the Arts.

[34] Iyer's recording Uneasy was listed among the best albums of 2021 in Pitchfork,[35] The New Yorker,[36] JazzTimes,[37] The Boston Globe, PopMatters,[38] and the ArtsFuse jazz critics' poll.

With Rez Abbasi With Burnt Sugar (led by Greg Tate) With Steve Coleman With Mike Ladd With Rudresh Mahanthappa With Roscoe Mitchell With Wadada Leo Smith With others