Mortelmans studied music at the Royal Flemish Conservatory in Antwerp, where his teachers included Peter Benoit, Joseph Tilborghs, and Jan Blockx, as well as Arthur De Greef (piano) and Hubert Ferdinand Kufferath (counterpoint).

In 1893, he was a winner of the Belgian Prix de Rome with his cantata Lady Macbeth.

From 1901, Mortelmans taught counterpoint and fugue at the Royal Flemish Conservatory, and became its director on 6 September 1924.

In 1903, with financial support from the patron François Franck, Mortelmans founded the Maatschappij der Nieuwe Concerten ("Society of New Concerts") in Antwerp, which attracted notable guest conductors and artists such as Gustav Mahler, Siegfried Wagner, Hans Richter, Richard Strauss, Sergei Rachmaninoff, Pablo de Sarasate, Jacques Thibaud, Pablo Casals, and Fritz Kreisler.

Mortelmans was also a founder of the organisation NAVEA, which is now SABAM (Société d'Auteurs Belge - Belgische Auteurs Maatschappij).