The School of University Studies and Doctoral Research can be traced back in its conception, in the fields of discipline of law and medicine, to the Ferdinand I College founded in 1593 to admit students of the Faculties of medicine and law, and to the Puteano College, founded in 1605 to admit students of the Faculties of medicine, law and philosophy who came from the town of Biella. These institutions were later refounded with the establishment in 1931 of the Mussolini College for Corporative Sciences and the National Medical College in 1932, both of which were linked to the Scuola Normale Superiore. In 1951 the Antonio Pacinotti College was also established to welcome students from the Faculties of Economics, Engineering and Agriculture. By Law No. 117 of 7 March 1967, the various colleges constitute a single "Higher School of University Studies and Specialization", organized in the disciplinary areas of Social Sciences and Applied and Experimental Sciences.

In 1987 the project for the enhancement of the training of excellence and collegiate realities is fully fulfilled in the Law n.41 of February 14, which establishes the birth of the School of University Studies and Doctoral Research. The Scuola Superiore Sant'Anna thus becomes the second Higher School of Pisa, on the model of the Scuola Normale Superiore, and is dedicated to the study of applied sciences: Economic and managerial sciences, Legal Sciences, Political Sciences, Agricultural Sciences and Plant Biotechnology, Medical Sciences and Industrial and Information Engineering.
At the same time, the School becomes part of the Italian university system as a university with a special order. Its headquarters is the Sant'Anna Conservatory, established in Pisa in 1785 by Grand Duke Pietro Leopoldo of Lorraine.
Over the years the Sant’Anna School of Advanced Studies has achieved not only national but also international relevance in the academic and scientific panorama, in line with challenges presented by the cultural, social, technological and scientific context.