Delvaux was born in Anheit in the Belgian province of Liège, the son of a lawyer. The young Delvaux took music lessons, studied Greek and Latin, and absorbed the fiction of Jules Verne and the poetry of Homer. All of his work was to be influenced by these readings, starting with his earliest drawings showing mythological scenes. He studied at the Brussels Academie des Beaux-arts, albeit in the architecture department owing to his parents' disapproval of his ambition to be a painter. Nevertheless Delvaux pursued his goal, producing naturalistic landscapes and having his first solo exhibition in 1925.

In 1926 Delvaux first encountered the metaphysical art of Giorgio de Chirico, which impressed him greatly, although Delvaux was then painting compositions featuring nudes in landscapes of an idyllic nature, and his work would not show de Chirico's influence for several more years. Delvaux found further inspiration in visits to the Brussels Fair, where the Spitzner Museum, a museum of medical curiosities, had a booth in which skeletons and a mechanical Venus figure were displayed in a window with red velvet curtains. This spectacle captivated Delvaux, supplying him with motifs that would appear throughout his work after 1934. In the mid-1930s Delvaux also began to adopt some of the motifs of his fellow Belgian Rene Magritte, as well as that painter's deadpan style in rendering the most unexpected juxtapositions of otherwise ordinary objects.

Although Delvaux associated for a period with the Belgian surrealist group, he thought of his art as a renewed classicism through which to convey the poetry and mystery of modern life. The paintings Delvaux became famous for usually feature numbers of nude women who stare as if hypnotized, gesturing mysteriously, sometimes reclining incongruously in a train station or wandering through classical buildings, accompanied by skeletons or puzzled scientists. Delvaux would repeat variations on these themes for the rest of his long life, although some departures can be noted. Among them are his paintings of 1945-47, rendered in a flattened style with distorted and forced perspective effects, and the series of crucifixions and deposition scenes enacted by skeletons, painted in the 1950s.

In the late 1950s he produced a number of night scenes in which trains are observed by a little girl seen from behind. These compositions contain nothing overtly surrealistic, yet the clarity of moonlit detail is hallucinatory in effect. Trains had always been a subject of special interest to Delvaux, who never forgot the wonder he felt as a small child at the sight of the first electric trams in Brussels.

In 1959 he executed a mural at the Palais du Congrès in Brussels, one of several large scale decorative commissions Delvaux undertook. He was named director of the Académie royal des Beaux-arts of Belgium in 1965. In 1982 the Paul Delvaux Museum opened in Saint-Idesbald. Delvaux died in Veurne in 1994.