Souto de Moura was born in Porto, and studied sculpture before switching to architecture at the School of Fine Arts of the University of Porto, the current FAUP – Faculdade de Arquitectura da Universidade do Porto, and receiving his degree in 1980. From 1974 to 1979 he worked with Álvaro Siza Vieira at his architectural practice, who encouraged him to start his own firm. He began his career as an independent architect in 1980, after winning a design competition for the Casa das Artes, a culture center with an auditorium and an exhibition gallery in the gardens of a neo-classical mansion, in his native city of Porto. However, Souto de Moura collaborated with Siza on the Portuguese pavilion at the Expo 2000 in Hanover, Germany, and Serpentine Gallery's annual summer pavilion in 2004.
Souto de Moura's early commissions were often modest residential houses, mainly in his native country. Later, he was commissioned with shopping centers, schools, art galleries, and a cinema, in countries including Spain, Italy, Germany, the United Kingdom, and Switzerland. Between 1989 and 1997, Souto de Moura spent eight years on the restoration Santa Maria do Bouro, a half-destroyed 12th-century monastery in Amares, transforming it into a Pousada.
From 1981 to 1990, Souto de Moura was assistant professor at his alma mater, and was later appointed Professor at the Faculty of Architecture at the University of Porto. He has been visiting professor at the architectural schools of Geneva, Paris-Belleville, Harvard University, Dublin, ETH Zurich and Lausanne, and has participated in numerous seminars and given many lectures both in Portugal and abroad. His work has appeared in various publications and exhibitions.
He has been also awarded: The Pessoa prize in 1998; the António de Almeida Foundation prize; the Antero de Quental Foundation prize; first prize in the Competition for the Restoration of Giraldo Square in Évora, Portugal; first prize in the Competition for the CIAC Pavilions; first prize in the Competition for a Hotel in Salzburg, Austria; first prize in the "IN/ARCH 1990 for Sicily" Competition; the Secil Prize for Architecture; second prize in the "Architecture and Stone" ideas competition; honourable mention for his Miramar House in the Secil Architectural Prizes; honourable mention for both the SEC Cultural Centre and the Alcanena House in the National Architectural Prizes. On 14 July 2011, Souto de Mouro received an Honoris Causa doctorate by the Faculty of Architecture and Arts at the Lusíada University of Porto.