Manos Hadjidakis was born in 1925, in Xanthi, Greece. At the age of four he began taking piano lessons and also learned to play the violin and the accordion. In 1932, the mother and her two children, Manos and Miranda, settled in Athens and the parents divorced. In 1938, his father was killed in an air accident. During theyears of German occupation and after the liberation, Hadjidakis worked as a stevedore in Piraeus, as an ice seller, a worker in the Fix Brewery, an employee in a photographic studio, and assistant male nurse in Military Hospital. Simultaneously, he took advanced courses in musical theory. At this time he was nurtured by artists and intellectuals of the generation between the two World Wars (George Seferis, Odysseas Elytis, Angelos Sikelianos, Yannis Tsarouhis, Nikos Gatsos), who contributed greatly to the way his orientations and thought took shape.
In 1945, he starting his collaboration with the Greek National Theatre and the Art Theatre of Athens. He mainly composed music for ancient Greek drama, as well as incidental music for the contemporary repertory. 
In 1949, together with Rallou Manou and the painter Spiro Vassiliou, he founded the Greek Dance Theatre Company with which he presented in public four ballets.
Beside his work for the theatre, from 1946 on, Manos Hadjidakis composed music for eighty Greek and foreign films. In 1960 he was awarded an Oscar for his music in Never on Sunday by Jules Dassin.
During the period 1966-72 he lived in New York, where he wrote some of his most important works, i.e. Rhythmology, Magnus Eroticus and Reflections. In the United States he started out writing The Era of Melissanthe, a musical chronicle of his life.
Manos Hadjidakis founded and directed the Athens Experimental Orchestra (1964-1971), the Musical Contests in Corfu (1981), and also, the cultural magazine Tetarto (1982), the record company Sirius (1985), the symphonic ensemble Orchestra of Colours (1989), and he directed the Third Programme of Greek National Radio (1975-81).
He died on June 15, 1994 in Athens.