Lyle David Mays was born on November 27, 1953, in Wausaukee, Wisconsin, and grew up in rural Wisconsin with four enthusiasms: chess, mathematics, architecture, and music. His mother, Doris, played piano and organ, and his father, Cecil, a truck driver, taught himself guitar by ear. He played organ at a relative's wedding at nine and in church at fourteen, and a piano teacher let him spend part of each lesson improvising. In his last year of high school, at a summer national stage band camp in Normal, Illinois, he met the pianist Marian McPartland. Two 1968 records shaped him: Bill Evans's live album from the Montreux festival and Miles Davis's Filles de Kilimanjaro.

Mays studied at the University of Wisconsin-Eau Claire and then transferred to what is now the University of North Texas, where he wrote and arranged for the school's One O'Clock Lab Band. He composed and arranged the band's album Lab 75, which was nominated for a Grammy Award, and after leaving North Texas he toured the United States and Europe for about eight months with Woody Herman's Thundering Herd. He first recorded the piece he called "Mars," later retitled "Close to Home," in 1977 with the Dallas fusion band High Rise.

In 1975 Mays met the guitarist Pat Metheny at the Wichita Jazz Festival, and the two soon became partners. He is the pianist on Metheny's ECM album Watercolors (1977), and in 1977 the Pat Metheny Group formed around Metheny, Mays, bassist Mark Egan, and drummer Danny Gottlieb. ECM issued Pat Metheny Group in 1978, and its follow-up American Garage (1979) reached number one on Billboard's jazz chart. Over the group's thirty-three years Mays was its pianist, keyboardist, sound designer, and principal co-writer; he and Metheny composed and arranged nearly all of its music, and Mays won eleven Grammy Awards with it. Among the pieces they wrote together are "Are You Going with Me?" (recorded in October 1981 for Offramp) and the title piece of Imaginary Day, while his own "Distance" appears on Still Life (Talking) (1987). He played trumpet on two tracks of First Circle (1984) and, now and then, accordion, autoharp, and electric guitar. The Way Up (2005), a single long-form work, was the group's last studio album, followed by a short Japan tour in 2008 and 2009 and a European "Songbook Tour" in 2010.

Away from the group, Mays made As Falls Wichita, So Falls Wichita Falls (1981) with Metheny and the percussionist Naná Vasconcelos, then four albums of his own. Lyle Mays (Geffen, 1986) and Street Dreams (1988) extend the group's keyboard and orchestral writing, the latter with a brass section, strings, and guests including Bill Frisell, Steve Gadd, and Peter Erskine. Fictionary (1993) is an acoustic piano trio with bassist Marc Johnson and drummer Jack DeJohnette, and Solo: Improvisations for Expanded Piano (Warner Bros., 2000) is a record of solo piano. He also led a quartet with Johnson, drummer Mark Walker, and saxophonist Bob Sheppard, scored children's audiobooks for Rabbit Ears (including The Tale of Peter Rabbit read by Meryl Streep), wrote music with Metheny for Steppenwolf Theatre's 1985 production of Orphans, and composed concert pieces such as "Twelve Days in the Shadow of a Miracle" for harp, flute, viola, and synthesizer, recorded by the Debussy Trio in 1996.

After the 2010 tour he retired from public performing, appearing only at a few events, and said in a 2016 interview that he had been working as a software development manager. In his last months he recorded "Eberhard," a thirteen-minute piece for large ensemble that revises a 2009 composition first heard at Lawrence University into a tribute to the German bassist Eberhard Weber; the sessions ran from August 2019 to January 2020. Mays passed away in Los Angeles on February 10, 2020, at age 66, after a long struggle with a recurring illness. "Eberhard" was released on August 27, 2021, and in 2022 it won the Grammy Award for Best Instrumental Composition.

Mays treated acoustic piano and synthesizers as parts of one orchestral palette, and his work ranges from pastoral, long-breathed fusion with the Pat Metheny Group to tightly written acoustic trio jazz and solo improvisation. He considered himself more a serious contemporary composer than a jazz pianist, with an advanced approach to harmony and form, and his larger structures include "Alaskan Suite," the extended design of The Way Up, and "Eberhard." The Oberheim synthesizer was a signature of his sound, and he worked with the instrument makers Kurzweil and Korg on new tones. Bill Evans was a lasting reference for him and Metheny alike; their piece "September Fifteenth" is named for the day Evans died. An AllMusic reviewer heard the heavy shadow of Keith Jarrett in his acoustic piano solos on his first solo album. "Close to Home" was recorded by Earth, Wind & Fire on Heritage (1990), and the Brazilian singer Milton Nascimento set it with Portuguese lyrics. Mays was also an amateur architect who admired Frank Lloyd Wright, and he designed his own house and studio.