He entered the Paris Conservatoire in 1904, where he studied with Louis Diémer and Lazare Lévy (piano), Alexandre Guilmant and Louis Vierne (organ), and Charles-Marie Widor (fugue and composition). In 1914, Dupré won the Grand Prix de Rome for his cantata, Psyché. In 1926, he was appointed professor of organ performance and improvisation at the Paris Conservatoire, a position he held until 1954.
Dupré became famous for performing more than 2000 organ recitals throughout Australia, the United States, Canada and Europe, which included a recital series of 10 concerts of the complete works of Johann Sebastian Bach in 1920 (Paris Conservatoire) and 1921 (Palais du Trocadéro), both performed entirely from memory. The sponsorship of an American transcontinental tour by the John Wanamaker department store interests rocketed his name into international prominence. Dupré's "Symphonie-Passion" began as an improvisation on Philadelphia's Wanamaker Organ. In 1924, he was elected as an honorary member of Phi Mu Alpha Sinfonia Fraternity, by the Fraternity's Alpha Chapter at the New England Conservatory in Boston.
In 1934, Dupré succeeded Charles-Marie Widor as titular organist at St. Sulpice in Paris, a post he held until his death in 1971.
From 1947 to 1954, he was director of the American Conservatory, which occupies the Louis XV wing of the Château de Fontainebleau near Paris. In 1954, Dupré succeeded Claude Delvincourt as director of the Paris Conservatoire, where he remained until 1956. He died in 1971 in Meudon (near Paris) at the age of 85.
As a composer, he produced a wide-ranging oeuvre of 65 opus numbers, and also taught two generations of well-known organists such as Jehan Alain and Marie-Claire Alain, Jean-Marie Beaudet, Pierre Cochereau, Jeanne Demessieux, Rolande Falcinelli, Jean-Jacques Grunenwald, Jean Guillou, Jean Langlais, Carl Weinrich and Olivier Messiaen, to name only a few. Aside from a few fine works for aspiring organists (such as the 79 Chorales op. 28) most of Dupré's music for the organ ranges from moderately to extremely difficult, and some of it makes almost impossible technical demands on the performer (e.g., Évocation op. 37, Suite, op. 39, Deux Esquisses op. 41, Vision op. 44).
His most often heard and recorded compositions tend to be from the earlier years of his career. During this time he wrote the Three Preludes and Fugues, Op. 7 (1914), with the First and Third Preludes (in particular the G minor with its phenomenally fast tempo/figurations and pedal chords) being pronounced unplayable by no less a figure than Widor. Indeed, such is their difficulty that Dupré was the only organist able to play them until several years later.
In many ways Dupré may be viewed as a 'Paganini' of the organ - being a virtuoso of the highest order, he contributed extensively to the development of technique (both in his organ music and in his pedagogical works) although, like Paganini, his music is relatively unknown to musicians other than those who play the instrument for which the music was written. A fair and objective critique of his music should take into account the fact that, occasionally, the emphasis on virtuosity and technique can be detrimental to the musical content and substance. However, his more successful works combine this virtuosity with a high degree of musical integrity, qualities found in works such as the Symphonie-Passion, the Chemin de la Croix, the Preludes and Fugues, the Esquisses and Évocation, and the Cortège et Litanie.
As well as composing prolifically, Dupré prepared study editions of the organ works of Bach, Handel, Mozart, Liszt, Mendelssohn, Schumann, César Franck, and Alexander Glazunov. He also wrote a method for organ (1927), 2 treatises on organ improvisation (1926 and 1937), and books on harmonic analysis (1936), counterpoint (1938), fugue (1938), and accompaniment of Gregorian chant (1937), in addition to essays on organ building, acoustics, and philosophy of music. As an improviser, Dupré excelled as perhaps no other did during the 20th century, and he was able to take given themes and spontaneously weave whole symphonies around them, often with elaborate contrapuntal devices including fugues. The achievement of these feats was partially due to his unsurpassed genius and partially due to his hard work doing paper exercises when he was not busy practising or composing.
Although his emphasis as composer was the organ, Dupré's catalog of musical compositions also includes works for piano, orchestra and choir, as well as chamber music, and a number of transcriptions. Some works initially published by HW Gray and now out of print have begun to be reissued by Crescendo Music Publications.