Pousseur studied at the Academies of Music in Liege and in Brussels from 1947 to 1953. He was closely associated with Pierre Froidebise and Andre Souris. He encountered Pierre Boulez, Karlheinz Stockhausen and Luciano Berio and thereafter devoted himself to avant-garde research.In 1954 he married Thea Schoonbrood with whom he had four children: Isabelle (1957), Denis (1958), Marianne (1961), and Helene (1965).
Beginning around 1960, he collaborated with Michel Butor on a number of projects, most notably the opera Votre Faust (1961-68). Pousseur has taught in Cologne, Basel, and in the United States at SUNY Buffalo, as well as in his native Belgium. From 1970 until his retirement in 1988 he taught at the University and Conservatory of Liege where he also founded the Centre de recherches et de formation musicales de Wallonie.Generally regarded as a member of the Darmstadt School in the 1950s, Pousseur's music employs serialism, mobile forms, and aleatory, often mediating between or among seemingly irreconcilable styles, such as those of Schubert and Webern (Votre Faust), or Pousseur's own serial style and the protest song "We shall overcome" (Couleurs croiscees).
His electronic composition Scambi (Exchanges), realized at the Studio di Fonologia in Milan in 1957, is unusual in the tape-music medium because it is explicitly meant to be assembled in different ways before listening. When first created, several different versions were realized, two by Luciano Berio, one by Marc Wilkinson, and two by the composer himself (Sabbe 1977, 175, n. 86). Since 2004, the Scambi Project, directed by John Dack at the Lansdown Centre for Electronic Arts at Middlesex University, has focussed on this work and its multiple possibilities for realization.In addition to his compositional and teaching activities, Pousseur has published many articles and ten books on music, amongst which are Fragments Theorique I: sur la musique experimentale (Brussels: Universite Libre de Bruxelles, 1970), Schumann le Poete: 25 moments d'une lecture de Dichterliebe (Paris: Klincksieck, 1993), and Musiques croisees (Paris: L'Harmattan, 1997).
He died aged 79, on the morning of 6 March 2009, of bronchial pneumonia.