Fuksas was born in Rome in 1944. At the beginning of the 1960s, he worked for Giorgio De Chirico in Rome. After he left Italy and worked for a period for Archigram in London, for Henning Larsen and for Jørn Utzon in Copenhagen. He received his degree in architecture from the La Sapienza University in 1969 in Rome, where he opened his first office in 1967, the GRANMA, collaborating with his first-wife Anna Maria Sacconi. From 1985 he has worked in partnership with his second wife, Doriana Mandrelli, who graduated in Architecture in Paris in 2007. Subsequent offices were opened in Paris (1989) and Vienna (1993), Frankfurt (2002) and Shenzhen, China (2008). Shenzhen Bao'an International Airport's new Terminal 3, which his firm designed and built 2008-2013 (with parametric design support by the engineering firm Knippers Helbig), is an outstanding example for the use of parametric design and production technologies in a large scale building. For many years he has dedicated his special attention to the study of urban problems and in particular to the suburbs. From June 1997 he was advisor to the I.F.A. (Institut Français d'Architecture) Administration Board. Since January 2000, he writes the architecture column of the weekly publication L'Espresso, established by Bruno Zevi. In 2000 he was (somewhat ironically in light of his practice of employing unpaid interns for periods up to two years) the Director of The Venice Biennale's - 7th International Architecture Exhibition - "Less Aesthetics, More Ethics".

He is visiting professor at several universities, including the École spéciale d'architecture in Paris, and Columbia University in New York.