At the age of four he was taught violin in Chioggia, and his grandfather noticed the young boy was a genius; Madame de Polignac (a French princess and patron) paid his following studies, so at the age of eight he was able to conduct the orchestras of La Scala and Arena di Verona. From here, he started a career as a child prodigy, internationally known as "Brunetto" (Italian for Little Bruno).
He protracted his studies in Milan (1935), Venice (1939) and in Rome (1940), where he finally took his degree in composition and musicology at the Accademia Nazionale di Santa Cecilia under the guide of Alessandro Bustini and Antonio Guarnieri. After his degree he studied also composition with Gian Francesco Malipiero and conducting with Hermann Scherchen.
During World War II he joined the army, the Partisan Resistance and he was also imprisoned in a concentration camp. After the war years, he taught composition at the Venice Conservatory from 1947 to 1950, where he was called by Malipiero; here he studied a lot the ancient and medieval music, which was the base for many of his early works. In those years he held a very big class, in which there was also Luigi Nono (at that time only a young law student). Karl Amadeus Hartmann called him to conduct a concert in the "Musica Viva" festival in Munich; this was the first time a foreign director was called, and for Maderna it was the beginning of a fabulous career. Whilst at the (1951) Internationale Ferienkurse für Neue Musik in Darmstadt he founded the Internationales Kranichsteiner Kammer-Ensemble; here he met, among others, Boulez, Messiaen, Stockhausen, Cage, Pousseur and the most important players of the neue musik that inspired him to compose new pieces (for example he wrote Musica su due dimensioni for Severino Gazzelloni).
Maderna was an eclectic director, so he was able to switch between different musical styles: he directed Purcell's Dido and Aeneas, Wagner's Parsifal, many works by Debussy and Ravel, classical and romantic symphonies; he also liked jazz music. Together with Luciano Berio, he founded the Studio di Fonologia Musicale of the RAI (Radiotelevisione Italiana) in 1955 and they also organized the Incontri Musicali music review and concert series.
In 1957-58 he taught dodecaphonic technique at the Milan Conservatory; in this period he also taught composition seminars at the Dartington's Summer School of Music. In 1963 he became a German citizen. From 1967 to 1970 he taught conducting at the Salzburg Mozarteum and also at the Rotterdam Conservatory. In 1970 he obtained the Darmstadt's citizenship (but he never changed his Italian citizenship for the German one). In 1971 and 1972 he was the Tanglewood (MA, USA) Berkshire Music Center's director. In 1971 he became the Milan RAI Symphony Orchestra's director.
As mentioned before, the flutist Severino Gazzelloni inspired Maderna during the Darmstadt experience. In those years he was obviously influenced also by the electronic music new paradigm. In 1961 he composed Honeyreves for flute and piano: this piece was built on the complex flute melodies and on the strange piano sound effects (clusters, playing on the strings, etc.). In the Studio di Fonologia Musicale, with the help of the sound technician Marino Zuccheri, he wrote some of the most impressive electroacustic works of his time: Musica su due dimensioni (Music on two dimensions, 1958) for flute and magnetic tape, Notturno (1956) and Continuo (1958) both for magnetic tape.
Maderna's favorite solo instrument was the oboe: this was the perfect 'aulodic' media that he was searching in order to build the 'absolute melody' (Aulody is a word that mixes the Greek aulos (i.e. oboe) and melody). In 1962-63, he wrote the first concert for oboe (Konzert fur Oboe und Kammerensemble), in which he was influenced by serial composition; in 1967 he wrote the second Concerto per oboe, in 1973 he wrote the Terzo Concerto per Oboe.
One of his most famous works was Quadrivium for four percussionists and four orchestra's groups (played for the first time at the Royan Festival, in 1969). This masterpiece uses an enormous amount of players, and is influenced by the aleatory technique. The aleatory technique is used also in Ausstrahlung for female voice, flute and oboe obbligati, big orchestra and magnetic tape (Irradiation, 1971, a homage to Persian culture), in Serenata per un satellite for — ad libitum — violin, flute, oboe, clarinet, marimba, harp, guitar and mandolin (Serenata for a Satellite, 1969) and in Grande Aulodia for flute and oboe soli with orchestra (1970). Among the other compositions, we find an electroacustic divertimento called Le Rire (1964), many Sonatas, an incomplete opera called Hyperion, and other diverse works.
A sign of Maderna's eclecticness was the fact that he also wrote music for five Italian movies released between 1946 and 1968. One of his pieces was featured in the soundtrack of 2001: A Space Odyssey, but his name was not in the film credits.