His early projects attracted considerable attention, and by 1953 he had become a visiting professor at the Illinois Institute of Technology under Mies van der Rohe. Mangiarotti returned to Italy in 1955, where he went into partnership with industrial designer Bruno Morassuti. In 1956, Mangiarotti and others founded the Associazione di Disegno Industriale (ADI), the professional organization that awards the famous Premio Compasso d'Oro.

Mangiarotti worked alone after 1960. His International Style buildings became known for their innovative structural systems similar to those of Pier Luigi Nervi. He was especially interested in materials and industrial production techniques. He carried out a great deal of research in these fields, eventually designing a number of prefabricated structural components in reinforced concrete. His technological expertise is evident in much of his furniture, including a 1963 plastic chair for Cassina, and the 1969 IN chair, manufactured by Zanotta from a single piece of self-surfaced polyeurathane.

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