After studying with Duilio Cambellotti at the Academy of Fine Arts in Rome, from which Prampolini was expelled for publishing an anti-academic manifesto, he became a leading exponent of the Futurist movement as a painter, set designer and architect. He had close contacts with representatives of European avant-garde art, with the Section d'Or, Dadaism, the Bauhaus, De Stijl, the Abstraction-Création group, with Pablo Picasso, Piet Mondrian, Wassily Kandinsky and Jean Cocteau. In 1917 he realised the sets for the futurist film Thaïs, directed by Anton Giulio Bragaglia. He created the interior of a dream and suffocating villa, whose walls are decorated with spirals, lozenges, chessboards and symbolic figures. This film had a significant influence on the anti-naturalistic scenes of German Expressionism.
Prampolini's work occupies a place of its own in the European abstract art, characterized by its deep concern for the dynamism and Organicism , which manifests itself in the cosmic visions and dreams of the 1930s and 1940s.
After the futurist experience, he produced different materials and works, sometimes influenced by the visions of the microcosm. He declared that his aim to express the extreme latitudes of the introspective world. In 1944 he taught theatre and set design at the Brera Academy in Milan.