Camilleri was born in Ħamrun and, as a teenager, had already composed a number of works based on folk music and legends of his native Malta. At the age of eighteen, he abandoned a career in law for that of music. He had already, at only fourteen, experienced the fact that some of his marches played at local feasts. In 1948 he went to London for a Promenade concert at the Royal Albert Hall. Two years later, in Australia he realised his ambition of being totally devoted to music, first as a student and later as a teacher. He subsequently visited Japan, Hong Kong and Korea.
He moved from his early influences by Maltese folk music to a musical form "in which nothing is fixed and his compositions evolve from themselves with a sense of fluency and inevitability". He composed over 100 works for orchestra, chamber ensemble, voice and solo instruments.
Camilleri's work has been performed throughout the world and his research of folk music and improvisation, the influences of the sounds of Africa and Asia, together with the academic study of European music, helped him create a "universal" style. His Little African Suite, written for piano and the Three African Sketches were purely studies in African music. These utilised both direct quotation and parody of ethnic music from the hinterland of the African continent, namely Congo, Chad and Ethiopia.
The Malta Suite was written when he was only fifteen years old, while holidaying in Gozo. He was quoted as saying that I was then as I am now, much in love with the folk music of the Maltese Islands known as għana. Its four sections are Country Dance, Waltz, Nocturne and Village Festa. This suite was featured in the album Malta: the music of Charles Camilleri, that was released by the Enterprise label in 1970, where the music was played by the New London Orchestra under the leadership of Patrick Halling and conducted by Maestro Joseph Sammut.After majoring in composition at the University of Toronto in Canada, he returned to Europe.
Camilleri is recognized as one of the major composers of his generation. His works include the now famous Malta Suite, Maltese Dances, A Maltese Overture - Din l-Art Helwa, operas in Maltese, a ballet based on the Knights of Malta and the oratorio Pawlu ta' Malta. His piano piece Cantilena, is currently part of the Grade 5 Trinity Guildhall piano syllabus. The Missa Mundi for solo organ was described by its first publisher as "the organ's Rite of Spring".
Writing in July 1973 to Turkish producer Ates Orga, then a member of the BBC Music Division, Camilleri expressed that at its best moments, music, for me, is a means to understand the complexity of man and the simplicity of God. Music is a way to reach the Supreme Being. His oratorio Pawlu ta' Malta, the first in the Maltese language, was performed to the lyrics of Oliver Friggieri at St. John's Co-Cathedral in 1985 with the participation of soprano Antoinette Miggiani, tenor Brian Cefai and baritone Lino Attard, together with the St. Julians Choir.
In 1998 Camilleri co-authored, together with folklorist Ġużè Cassar Pullicino, the book Maltese oral poetry and folk music, published by the University of Malta. The publication focused on the different models of Maltese folksinging and a brief introduction to Maltese nursery rhymes, street cries and traditional folk instruments. Christopher Palmer had, in 1975 written a critical biography of the composer, through The music of Charles Camilleri : an introduction.
Camilleri died on 3 January 2009 at the age of 77. His funeral took place two days later at Naxxar, his long-time town of residence. Flags across Malta were flown at half-mast in a national tribute to him.