Like his brother, Harry Gregson-Williams, Rupert was a lead chorister in one of Britain's great traditional academic church choirs, that of St. John's College, Cambridge. In return for singing with the choir at daily services during school term and touring with it around the world, he received a scholarship to St. John's College's preparatory school and entrance to Cambridge. Unlike Harry, who graduated from the Guildhall School of Music and Drama, Rupert admits to being a rebellious student who got thrown out of school more than once. He believed that he had all the basic knowledge he needed and went to work as a professional musician, mostly in rock & roll bands, after a stint as a teacher in Africa.

A friendship with composer Richard Harvey, which grew from their shared interest in ethnic music and instruments, led him into film music. Rupert had been intrigued by the use of classical music in film since Visconti used Mahler's music in Death in Venice, and was happy to assist Harvey after the latter got some work scoring for British television projects. The two worked together in collaboration with Elvis Costello on G.B.H. and Jake's Progress, two films directed by Alan Bleasdale. In the process, Rupert learned much about advanced orchestration. His first original score was for an independent film by Genevieve Jolliffe, called Urban Ghost Story, which was a coming of age drama rather than a horror picture. Rupert composed an intimate score, mainly for solo piano and flutes, but of a substantial length at 50 minutes. Following that, the established film composer Hans Zimmer asked him to join his organization Media Ventures, which provided music for film, television, advertisements, and other commercial uses, including the two-minute piece Rupert wrote for the World Cup soccer finals in Japan. Gregson-Williams worked directly with Zimmer on the score to The Prince of Egypt, composing certain sequences in the film using Zimmer's melodies to the composer's specifications. Other film and television projects on which Gregson-Williams has worked include El Dorado, Virtual Sexuality, Muppets from Space, Extremely Dangerous, and Hannibal.

Brother Harry then went to work for Media Ventures' Los Angeles operation, while Rupert mostly worked from his 15th century Sussex countryside home. The two brothers collaborated on the score for Jerry Bruckheimer's film Swing Vote in 2008. Rupert used Macintosh MIDI equipment and was fond of Steinberg's Cubase sequencing software, which allowed him to produce an accurate, synthesized version of a cue to play for a director before orchestrating and recording it. ~ Joseph Stevenson