Delvaux's paintings of the late 1920s and early 1930s, which feature nudes in landscapes, are strongly influenced by such Flemish Expressionists painters as Constant Permeke and Gustave De Smet. A change of style around 1933 reflects the influence of the surrealist art of Giorgio de Chirico, which he had first encountered in 1926 or 1927. In the early 1930s Delvaux found further inspiration in visits to the Brussels Fair, where the Spitzner Museum, a museum of medical curiosities, maintained 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.

In the mid-1930s he also began to become inspired by fellow Belgian painter  René Magritte, as well as that painter's style in rendering the most unexpected juxtapositions of otherwise ordinary objects.

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. Sometimes they are accompanied by skeletons, men in bowler hats, or puzzled scientists drawn from the stories of Jules Verne. 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 1959 he executed a mural at the Palais des Congrès in Brussels, one of several large scale decorative commissions Delvaux undertook. He was named director of the Académie royale des Beaux-arts in 1965. In 1982 the Paul Delvaux Museum opened in Saint-Idesbald, Belgium. Delvaux died in Veurne, Belgium in 1994.