Mark Ware Isham was born in New York City on September 7, 1951, the son of Patricia Hammond Isham, a violinist, and Howard Fuller Isham, a professor of humanities. He studied trumpet from early childhood, made his professional debut at twelve, and also studied piano and violin. When he was a teenager the family moved to the San Francisco Bay Area, where he played with the Oakland East Bay Symphony. His own biography says that by fifteen he was working jazz clubs while also playing with the Oakland and San Francisco symphonies.

The shape of his career should be stated plainly. Most of what he has released under his own name is electronic, ambient or new age music, and most of his working life since 1983 has gone into film and television scoring: Wikipedia counts more than 200 productions, and AllMusic calls film scoring his primary focus. The jazz side is a smaller part of the catalog but a documented one: two records for ECM with the pianist Art Lande, two quintet albums for Columbia in 1995 and 1999, and a 2009 standards album with the Australian singer Kate Ceberano.

In the 1970s he worked as a touring and session player. AllMusic lists the jazz leaders Pharoah Sanders and Charles Lloyd and the pop acts the Beach Boys and Van Morrison among his employers. His documented record credits from that period are narrower: synthesizer on Lloyd's Pathless Path (Unity, 1979) and on one track of Sanders's Journey to the One (Theresa, 1980). The central jazz work of the decade was Rubisa Patrol, the quartet Art Lande formed in 1976, which played around the Bay Area and toured Europe by van. Isham played trumpet, flugelhorn and soprano saxophone on Rubisa Patrol (ECM, recorded May 1976) with the bassist Bill Douglass and the drummer Glenn Cronkhite. The follow-up, Desert Marauders (recorded June 1977, released 1978), had Kurt Wortman on drums and includes Isham's composition "Livre (Near the Sky)." AllMusic hears a strong Miles Davis influence in his playing from this period.

From 1979 he was in Van Morrison's band. He played trumpet and flugelhorn on Into the Music (1979), where the horn arrangements are credited to him and Pee Wee Ellis, and he recommended Ellis to Morrison, who then stayed for the whole album. He appeared with Morrison at the Montreux Jazz Festival in 1980 and went on to Common One (1980), Beautiful Vision (1982) and the live album Live at the Grand Opera House Belfast (1984). In the same years he formed Group 87 with the guitarist Peter Maunu and the bassist Patrick O'Hearn, with the drummer Terry Bozzio also in the lineup. The band made two albums, Group 87 (Columbia, 1980) and A Career in Dada Processing (Capitol, 1984), and AllMusic describes its instrumental music as arriving years before new age became a category.

His solo career began in 1983 with Vapor Drawings, the first electronic record on the Windham Hill label. A demo he had circulated for ECM reached the director Carroll Ballard, who hired him for the Disney film Never Cry Wolf (1983), and the film work grew from there. At the same time he kept playing on other people's records, including David Sylvian's Brilliant Trees (1984), where he plays trumpet on one track, and Art Lande's duo album with him, We Begin (ECM, recorded January 1987). The late 1980s brought Castalia (Virgin, 1988) and Tibet (Windham Hill, 1989), both nominated for the Best New Age Performance Grammy, and then Mark Isham (Virgin, 1990), which won the Grammy for Best New Age Album at the 33rd Grammy Awards in 1991. He also composed the music for the Rabbit Ears children's storybook recordings, three of which brought Best Album for Children nominations. His scores include A River Runs Through It (1992, Robert Redford), which brought an Academy Award nomination for Best Original Score, Nell (1994, Golden Globe nomination), Quiz Show (1994, Redford), Blade (1998), Crash (2004, Paul Haggis), The Black Dahlia (2006, a best-score award from the International Film Music Critics Association) and the television series Once Upon a Time (2011 to 2018). He won a Primetime Emmy for the main title theme of EZ Streets, and in 2006 ASCAP gave him its Henry Mancini Award for lifetime achievement.

The jazz records returned in the mid-1990s. In 1992 he had premiered Five Stories for Trumpet and Orchestra with the St. Louis Symphony as soloist, and in 1995 Blue Sun (Columbia) introduced a working quintet of keyboardist David Goldblatt, saxophonist Steve Tavaglione, bassist Doug Lunn and drummer Kurt Wortman, playing mostly Isham originals. Miles Remembered: The Silent Way Project (Columbia, 1999) was recorded live at The Baked Potato in North Hollywood during 1996 with a twin-guitar electric band of Steve Cardenas and Peter Maunu, and plays music by Miles Davis and Joe Zawinul alongside two Isham pieces. Bittersweet (2009), an album of standards with Kate Ceberano, was recorded live without overdubs in three days at his home studio with the pianist Alan Pasqua, the bassist Tom Warrington and the drummer Peter Erskine, and was nominated for Best Jazz Album at the 2009 ARIA Awards. He has since played trumpet on records by Brian Wilson (No Pier Pressure, 2015), Stanley Clarke (The Message, 2018) and Joni Mitchell (Both Sides Now, 2000), is credited with Scott Steiner on the score of the Buddy Bolden film Bolden (2019, with music by Wynton Marsalis), and is credited on the 2021 release of the pianist Michael Wolff's Live at Vitello's, recorded in Los Angeles in August 2011. His most recent feature score listed in the sources is Soul on Fire (2025). A radio interview broadcast in February 2026 was recorded at his home studio in Hidden Hills, California.

Isham's trumpet playing carries the Miles Davis influence that AllMusic hears from his Rubisa Patrol years, and a reviewer of Blue Sun heard it in his Harmon-muted playing while finding his tone less fragile than Davis's. In a 1995 interview he described improvisation and composition as nearly the same act. He says he came to writing through electronics, starting on a Fender Rhodes before he owned a piano, and that for his quintet he works from lead sheets, bass lines and verbal descriptions of a section's mood rather than fully written parts. The electronic albums treat the trumpet as one color among synthesizers and processed instruments, and he describes film scoring as a matter of finding the turning points of a scene and writing the music from one to the next.

How the work is classified depends on which part you hear. Wikipedia lists his styles as crossover jazz, post-bop, ambient, progressive electronic, chamber jazz and new age, and AllMusic files him under stage and screen first. Only a minority of his output is jazz, and the film scores and Windham Hill records are not jazz at all. What connects the two worlds is the same instrumental voice and a working method based on improvisation, together with a circle of Bay Area and Los Angeles players (Douglass, Wortman, Lunn, Maunu, David Torn) who recur on records of both kinds.