Hart dropped out of high school as a senior. Impressed by its musical pedigree, he enlisted in the United States Air Force in 1961. He served as a drummer in The Airmen of Note, an elite big band unit in the United States Air Force Band modeled after Glenn Miller’s celebrated Army Air Forces Band.

While stationed in southern California, he had discovered that his father (by now employed as a savings and loan association executive in Los Angeles) was still involved in the drumming community as an endorser for Remo. Founder Remo Belli facilitated an introduction before Hart was reassigned to Spain, but the elder Hart soon disappeared. A post-discharge reconciliation attempt (also mediated by Belli) proved to be more successful. Shortly thereafter, father and son established the Hart Music Center in San Carlos, California. In late 1965 or early 1966, Hart performed in an early iteration of William Penn and His Pals prior to Gregg Rolie’s membership and the recording of the garage rock classic “Swami.” Later in 1966, Hart and Bennett briefly resumed their collaboration before the latter reenlisted for a tour of duty in Vietnam.

Hart joined the Grateful Dead in September 1967. His interests in polyrhythmic rudiments and exotic percussion were integral to the band’s arrangements in the period that archivist Dick Latvala would subsequently characterize as the “primal Dead era” of 1968–1969. However, he left by mutual agreement in February 1971, extricating himself after his father (who briefly managed the group) embezzled $70,000 from the band. In his 2015 memoir, Kreutzmann divulged that Hart’s use of heroin and other “dark drugs” had accelerated in the wake of the embezzlement and impacted his contributions to the group, also contributing to his departure: “Mickey wasn’t able to play at the level he was capable of and it was beginning to affect our performances. He was getting really spacey and just getting so far out there that he wasn’t able to deliver the music. It became impossible for me to play with him. It wasn’t out of anger or meanness, but we had to address it and deal with it. So our brother Mickey left the band and retreated to his ranch in Novato and it really strained our relationship for a while, sad to say.”

For three and a half years, he was stationed throughout Europe, where he also claimed to have taught “combative measures” (most notably judo, in which he had attained a black belt) to units of the Strategic Air Command and other units in Europe and Africa. During a tour in Spain, he reportedly sat in with a variety of notable jazz musicians (including Gerry Mulligan and Count Basie) in addition to performing in various ensembles (spanning the gamut from small jazz combos to marching bands) and on recording sessions for local pop stars. Hart would later intimate in a 1972 interview that his Airmen of Note assignment served as a “cover” for his instructive duties. While in the Air Force, he co-founded Joe and the Jaguars (alternatively billed as The Jaguars) with a fellow serviceman, guitarist Joe Bennett. Following his 1965 discharge, Hart briefly returned to the New York metropolitan area, where he filled in for the regular drummer in a “staid fox-trot band” as a member of the local musician’s union.

During his sabbatical, he released the album Rolling Thunder in 1972. Two additional solo albums (including an ambient music project that was envisaged as the soundtrack for The Silent Flute, a screenplay co-written by Bruce Lee, James Coburn and Stirling Silliphant that was ultimately filmed in 1978 as the David Carradine vehicle Circle of Iron) were completed but rejected by Warner Brothers due to the label’s increasingly strained relationship with the Grateful Dead. Hart’s home recording studio proved to be a haven for the more idiosyncratic endeavors pursued by various band members, and he continued to collaborate with his former bandmates on various projects, most notably Robert Hunter’s Tales Of The Great Rum Runners (1974) and Ned Lagin’s Seastones (1975).

He returned to the Dead for their final pre-hiatus concert in October 1974 (much to the initial chagrin of Kreutzmann, who soon reconciled with Hart) and was formally reinstated by the beginning of the group’s 1976 tour. He remained with the group until their official dissolution in 1995. Hart’s collaboration with the remaining members of the Grateful Dead has continued with The Other Ones, The Dead and Dead & Company.

In 1991, Hart produced the album Planet Drum, which remained at #1 on the Billboard World Music chart for 26 weeks, and received the first ever Grammy Award for Best World Music Album.

In 1994, Mickey Hart was inducted into the Rock and Roll Hall of Fame as a member of the Grateful Dead.

After the death of Jerry Garcia and the consequent dissolution of the Grateful Dead in 1995, Hart continued to play music with various groups including members of the Grateful Dead. In the 1996 Furthur Festival, Mickey Hart’s Mystery Box played, as did Bob Weir’s band Ratdog.

In 2000, Hart became a member of the Board of Directors of the Institute for Music and Neurologic Function, a nonprofit organization that studies the healing power of music – continuing his investigation into the connection between healing and rhythm, and the neural basis of rhythm. In 2003, he was honored with the organization’s Music Has Power Award, recognizing his advocacy and continuous commitment to raising public awareness of the positive effect of music.

In 2005, Hart and the members of the band Particle joined to create the Hydra Project.

During 2006, Hart teamed up with fellow Grateful Dead bandmate Bill Kreutzmann, Phish bassist Mike Gordon and former Other Ones lead guitarist Steve Kimock, to form the Rhythm Devils, a nickname that refers to Hart and Kreutzmann’s drum duets and improvisation. The band features songs from their respective repertoires as well as new songs written by Jerry Garcia’s songwriting companion Robert Hunter. The Rhythm Devils announced their first tour in 2006, which ended at the popular Vegoose festival in Las Vegas, Nevada over the Halloween weekend.

In 2010 Hart debuted “Rhythms of the Universe,” a composition based on a variety of astrophysical data. The composition represents a collaboration between scientist and artist, using their own sophisticated tools. Nobel Laureate in physics George Smoot from the University of California, Berkeley, and Lawrence Berkeley National Laboratory (LBNL), and Keith Jackson, a computer scientist and musician also from LBNL, are providing some of the data for the project. The final result will be a “musical history of the universe”, from the Big Bang onwards through galaxy and star formation, up until modern times, including images from the Hubble Space Telescope and rhythms derived from the cosmic background radiation, supernovae, quasars, and many other astrophysical phenomena. The work premiered at the conference “Cosmology on the Beach” in Playa del Carmen in January 2010.

In April 2010, it was announced that Rhythm Devils will tour in the summer of 2010 with a new lineup including Mickey Hart and Bill Kreutzmann (assorted percussion), Keller Williams (guitar, vocals), Sikiru Adepoju (talking drum), Davy Knowles (guitar, vocals), and Andy Hess (bass).

The Rhythm Devils did only one show in 2011, at the Gathering of the Vibes Music Festival in Bridgeport, Connecticut. This version of the band was Hart, Kreutzmann, Keller Williams, Sikiru, Steve Kimock and Reed Mathis of Tea Leaf Green on bass.

In 2011 Hart debuted a new version of the Mickey Hart Band. This lineup included Tim Hockenberry (vocals, keyboards, trombone, saxophone, other instruments), Crystal Monee Hall (vocals, guitar, hand percussion), Ben Yonas (keyboards), Gawain Mathews (guitar), Sikiru Adepoju (talking drum, djembe, shakers), Ian “Inkx” Herman (drums), Greg Ellis (percussion), Vir McCoy (bass). The band played a few shows in August 2011 on the east and west coasts of the United States. In November and December 2011, the Mickey Hart Band did a 17-date tour with a slightly modified lineup. McCoy and Ellis were not in this lineup, and Widespread Panic band member Dave Schools joined the band as their bass player for the tour.

On October 11, 2011, Smithsonian Folkways released The Mickey Hart Collection. Comprising 25 albums, the series includes music from regions that span the globe, including the Sudan, Nigeria, Tibet, Indonesia, Latvia, and Brazil.

In August 2013, the Mickey Hart Band embarked upon a tour with the Tea Leaf Trio, which includes three members of the band Tea Leaf Green, in support of the band’s album Superorganism.

On September 29, 2013, the completed version of his and George Smoot’s film Rhythms of the Universe premiered at the Smithsonian Air and Space Museum in Washington, D.C.

Also in 2015, Mickey began touring with Dead & Company, a band consisting of former Grateful Dead members Bob Weir, Mickey Hart and Bill Kreutzmann, along with John Mayer (guitar), Oteil Burbridge (bass), and Jeff Chimenti (keyboards). The band began touring in the Fall of 2015 and have conducted multiple Fall, Spring, and Summer tours since then. In 2017, he released RAMU, which featured contributions from both his longtime collaborators Steve Kimock and Sikiru Adepoju as well as Avey Tare and Tank Ball, among others