Paul Horn was born in New York City on March 17, 1930. His family moved to Washington, D.C., when he was four, the age at which he began piano; he took up the clarinet at 12, attended Theodore Roosevelt High School and the Washington College of Music, and played the city's jazz clubs as a teenager. He studied clarinet and flute at the Oberlin Conservatory of Music in Ohio, where he earned a bachelor's degree, and received a master's degree from the Manhattan School of Music in June 1953. He did not take up the flute until he was 19, and it became the instrument he most wanted to play only toward the end of the 1960s.

In 1956 he was hired as a tenor saxophonist by the big band co-led by Eddie Sauter and Bill Finegan, and in the same year he joined Chico Hamilton's quintet in Los Angeles, the chamber-flavored West Coast group built around a cello. He stayed until 1958. A version of the quintet with Horn appears on screen in the 1957 film Sweet Smell of Success, and the group's records from those years include Chico Hamilton Quintet (Pacific Jazz, 1957), Sweet Smell of Success (Decca, 1957) and South Pacific in Hi-Fi (World Pacific, 1958). His own first date as a leader, House of Horn for Dot, was recorded at Radio Recorders in Hollywood on September 27 and 30, 1957, with Fred Katz on cello, Gerald Wiggins on piano, Larry Bunker on vibraphone and Red Mitchell on bass. Plenty of Horn followed on Dot in 1958 with a larger group that included Shelly Manne on drums, Stu Williamson on trumpet and Mongo Santamaría on congas, and a Paul Horn Four album, Impressions!, came out on World Pacific the same year.

Through the late 1950s and early 1960s he was one of Los Angeles's busiest reed and flute players. He recorded with Fred Katz, with Buddy Collette's four-flute Swinging Shepherds (EmArcy, 1958), with Ken Nordine on the Word Jazz albums, and with Shorty Rogers and Pete Rugolo. He was on Cal Tjader's Concert by the Sea (Fantasy, 1959), recorded live in Carmel, California, under the leadership of Cal Tjader, and on Tjader's Latino!, recorded in 1960 and released in 1962. He took part in Duke Ellington's Swinging Suites by Edward E. and Edward G. (Columbia, 1960), became a member of the NBC staff orchestra, and played on Henry Mancini's More Music from Peter Gunn. The Guardian obituary lists singers he recorded with, including Nat King Cole, Frank Sinatra, Nancy Wilson and June Christy, and names Tony Bennett among the stars he worked with. He also worked in film and television: he scored the 1959 animated series Clutch Cargo, played the saxophone solo that opens Roger Corman's A Bucket of Blood (1959), and led his band in the club scene that opens Night Tide (1961).

His own quintet, with vibraphonist Emil Richards, pianist Paul Moer and a bassist and drummer that changed over the years, made a run of jazz albums that began with Something Blue (HiFi Jazz, recorded in March 1960, with Billy Higgins on drums) and moved to Columbia for The Sound of Paul Horn (1961), Profile of a Jazz Musician (1962) and Impressions of Cleopatra (1963). He was also the subject of a television documentary by David Wolper. For RCA Victor he recorded Jazz Suite on the Mass Texts, composed and conducted by Lalo Schifrin for his quintet, a brass section, harps, percussion and a choir, on November 5 and 6, 1964, with Horn as principal soloist on alto saxophone, flute and clarinet; it was released in 1965. Other RCA albums include Cycle (1965), Monday, Monday (1966), a set of pop and folk-rock songs of the day arranged mostly by Oliver Nelson, and the ballad collection Here's That Rainy Day (1966). Horn received five Grammy nominations between 1965 and 1999, three of them in 1965.

A practice of Transcendental Meditation led him away from that career. He studied with Maharishi Mahesh Yogi, was at the Maharishi's ashram in Rishikesh, India, in 1968 at the same time as the Beatles, and made two albums of Indian music for World Pacific, Paul Horn in India and Cosmic Consciousness: Paul Horn in Kashmir. While producing a documentary on the Maharishi he returned to India in April 1968 and, on April 25, recorded solo flute inside the Taj Mahal in Agra, where the dome holds an echo of nearly half a minute and a tomb guard answered with a few chanted calls. Inside was released by Epic in 1969, found a large audience without radio play, and was reported by the BBC in 2001 to have sold over a million copies; it is regularly named as a founding record of new age music. He followed it with Inside II (1972) and Inside the Great Pyramid (1977), recorded in the Great Pyramid at Giza, and went back to the Taj Mahal on March 1 and 2, 1989, for Inside the Taj Mahal II.

In 1970 Horn moved with his family to Victoria, British Columbia, on Vancouver Island, a step that DownBeat reported under a headline about his leaving the United States. He formed a new quintet, recorded film scores for the National Film Board of Canada, and hosted The Paul Horn Show on CTV, where he met the singer-songwriter Ann Mortifee in 1973. He toured China and the Soviet Union, in 1979 and 1983, and released albums from those trips on Golden Flute Records, the label he founded; played his flute for recordings with the killer whale Haida at the Sealand of the Pacific aquarium in Oak Bay; made Altura do Sol (Epic, 1976) with Egberto Gismonti and bassist Ron Carter; and recorded two duet albums with the Native American flutist R. Carlos Nakai, Inside Canyon de Chelly (1997) and Inside Monument Valley (1999). His autobiography, written with Lee Underwood, appeared in 1990 as Inside Paul Horn: The Spiritual Odyssey of a Universal Traveler. He was a frequent instructor at the Victoria Conservatory of Music's summer jazz workshop, and in the 2000s he began spending part of each year in Tucson, Arizona. Horn passed away at his condominium in Vancouver on June 29, 2014, at 84, after a brief illness. He was survived by his wife, Ann Mortifee, and his sons Marlen and Robin.

Horn's early records place him in the cool and West Coast jazz of the 1950s: a clear, accurate tone on flute, alto saxophone and clarinet, chamber-sized groups, and larger projects such as the Schifrin Mass setting. JazzTimes describes those early works as falling squarely into the bop and cool schools. The turn came in 1967 and 1968. Meditation, Indian music and the sound of large reverberant spaces pulled his playing toward slow, spacious improvisation that often set aside jazz rhythm and harmony, and the critic Joachim Berendt, quoted in The Guardian, likened the echo of the Taj Mahal to a hall of mirrors for sound. His later albums, many recorded on location or with players from other traditions in China, Russia, Brazil, Africa, Tibet and the American Southwest, are catalogued today as new age, ambient and world music. The Guardian notes that jazz critics dismissed that later work as weightless and that his serene records dropped out of jazz discographies after the mid-1990s, and it also credits his tone, accuracy and listening. The jazz years, roughly 1953 to 1966, are substantial and documented, yet the best-known part of his catalog lies outside them, which makes him a crossover figure: a working jazz soloist who became one of the first widely known names in new age music.