While studying oboe at Juilliard, he formed a rock-classical fusion band called New York Rock and Roll Ensemble, which appeared on the first of Leonard Bernstein's Young People's Concerts with the New York Philharmonic; it was Bernstein who introduced Kamen to symphonic arranging and composing.

Kamen's early creative work centered on ballets (he has written ten so far, for the Harkness Ballet, Louis Falco, Alvin Ailey, Joffrey Ballet and Milan's La Scala), but he expanded into Hollywood with his score for The Next Man in 1976 and into pop and rock arranging when he collaborated on the album The Wall by Pink Floyd three years later.

He has since established himself among the leading film composers, with scores for over seventy movies and television shows - including the Lethal Weapon and Die Hard series, Robin Hood: Prince of Thieves, 101 Dalmatians, Mr. Holland's Opus, The Winter Guest, X-Men, Frequency, Edge of Darkness, Brazil and The Iron Giant, as well as music for the Closing Ceremonies of the 1996 Summer Olympics - that have garnered two Oscar nominations, two Golden Globe Awards, three Grammys and an Emmy. (With Richard Dreyfuss, who was nominated for an Oscar for his role as the inspiring music teacher Mr. Holland, Kamen has established the not-for-profit Mr. Holland's Opus Foundation, dedicated to giving musical instruments to needy students.)

In addition, Kamen has created hit singles for such leading pop and rock artists as Bryan Adams (Everything I Do, I Do It For You and Have You Ever Really Loved a Woman, both Grammy winners), Sting (It's Probably Me), Rod Stewart, David Bowie and Eric Clapton. In recent years, he has created a synthesis of pop, rock, jazz, world and symphonic music with his orchestral settings featuring such stars as David Sanborn, Herbie Hancock and Eric Clapton, his symphonic arrangements of songs by Bob Dylan (for a 1994 concert benefiting UNESCO), an overture composed for 200 Buddhist monks, and pieces for the Kodo Drummers of Japan and The Chieftains.

In 1999, he conducted a program of his arrangements combining the rock group Metallica with symphony orchestra. The concert, titled S & M, was performed with the Orchestra of St. Luke's in New York City, the Berlin Philharmonic and the San Francisco Symphony Orchestra; the recording, with the San Francisco Symphony Orchestra, went multi-platinum. In January 2000, the National Symphony Orchestra premiered Kamen's "Millennium Symphony," The New Moon in the Old Moon's Arms, inspired by the vanished Anasazi tribes of the American Southwest.