Paul-Henri Büsser was born in Toulouse, of partly German ancestry. He entered the Paris Conservatoire in 1889, where he studied organ with César Franck and composition with Ernest Guiraud. Employed for a while as secretary to Charles Gounod he received valuable advice from that composer, who helped him obtain a job as organist at Saint-Cloud. In 1893 he won the Prix de Rome for music, and on his return from Italy he began a career as a conductor. At the personal request of Claude Debussy, Büsser led the fourth performance, and numerous subsequent performances, of Pelléas et Mélisande. He also became a protégé of Jules Massenet, and was one of the elder composer's closest friends during the last two decades of the latter's life (Massenet died in 1912).
In 1921 Büsser began teaching at the Paris Conservatoire, and was promoted to professor of composition in 1931. Noted students include Prix de Rome winner Henri Challan, the Japanese composer Tomojirō Ikenouchi (1906–1991) and Henri Dutilleux (1916-2013). The Académie française elected him as member in 1938. He married the famous dramatic soprano Yvonne Gall (1885–1972).
While Büsser composed a wide range of compositions, his most important works were for the stage. His operas include Daphnis et Chloé, Colomba and Les noces corinthiennes. Several stage works demonstrate his comic wit, especially Le carosse du Saint Sacrement and Roxelane as well as the farce Diaforus 60, an update of Molière's Le malade imaginaire. He composed in a sophisticated compositional style with finely crafted orchestration, but remained faithful to 19th-century French tradition.
His orchestrations of Debussy's Petite Suite and Printemps are considered standards, as is his crisp, authoritative conducting of the first nearly complete 1930 early electrical HMV recording of Gounod's Faust in French featuring the great tenor César Vezzani in the title role and the renowned bass Marcel Journet, who as a Metropolitan star had sung and recorded Méphistophelès' key arias and ensembles with Caruso on Victor acoustical records earlier in the century. These recordings have all been transferred.
Late in his life, the government of France made him a Grand Officier de la Légion d'honneur.
- Hélène, before 1890, incomplete
- Les accordailles, 1890, unperformed
- Jane Grey, 1891
- Les Marivaudages, 1891, unperformed
- Daphnis et Chloé, 1897
- Le miracle de perles, 1898, unperformed
- Blanc et noir, 1900
- Colomba, 1921
- Les noces corinthiennes, 1922
- La pie borgne, 1927
- Rhapsodie arménienne, 1930
- Le carrosse du Saint-Sacrement, 1948
- Roxelane, 1948
- Diafoirus 60, 1963
- La Vénus d'ille, 1964
- La ronde des saisons, 1905 (Paris Opera, choreography by Joseph Hansen)
- Appassionato, 1910
- Les trois sultanes, 1923
- Manon, 1925
- Histoire de France, 1929
- Piéce in E-flat for Trombone and Piano, Op. 33
- Appassionato for viola and piano, Op. 34, 1910
- Prelude et Scherzo for flute and piano, Op. 35
- Morceau de Concert (Concert Piece in D) for horn and piano, Op. 39
- Catalane sur des airs populaires for viola and orchestra or piano, Op. 78, 1926
- Rhapsodie arménienne for viola and piano, Op. 81, 1930
- La Chasse de Saint Hubert for horn and piano, Op. 99, ca. 1937
- "Andalucia" sur des thèmes Andalous Op.86 for flute and piano (Concours du Conservatoire National de Musique Paris)
- "Petite Suite" Op.12, for flute and piano.
- De Pelléas aux Indes galantes—De la flûte au tambour, (memoires), 1955
- Sadie, Stanley (Ed.)  (1994). The New Grove Dictionary of Opera, vol. 1, A-D, chpt: "Büsser [Busser], (Paul-) Henri" by Arthur Hoérée & Richard Langham Smith, New York: MacMillan. ISBN 0-935859-92-6.