IMT originated in 2004 thanks to the convergence and cooperation of three entities: the Inter-University Consortium of Advanced Studies (CISA) (formed by Università Luiss Guido Carli di Roma, Scuola Superiore Sant'Anna di Pisa and Politecnico di Milano), Università di Pisa and the Fondazione Lucchese per l'Alta Formazione e la Ricerca (Lucca Foundation for Advanced Studies and Research or FLAFR), supported by the Comune di Lucca, Provincia di Lucca, Fondazione Cassa di Risparmio di Lucca, Fondazione Banca del Monte di Lucca, Camera di Commercio di Lucca, and Associazione degli Industriali della Provincia di Lucca.

The first PhD program began on March 1, 2005, and the inauguration of the first academic year took place on March 5th of the same year. IMT was formally established by decree of the Ministry of Education, University and Research signed on November 18, 2005, and published in the Official Gazette, together with the statutes of the School, on November 30, 2005. It is an "institution of higher education of doctoral training with special ordinance". Fully integrated into the main public Italian university system, IMT is a legal entity with full scientific, didactic, organizational, managerial, administrative, and financial autonomy.

The first director and founder of IMT was Prof. Fabio Pammolli. Prof. Alberto Bemporad, who first joined the school in July 2011 as Full Professor of Control Systems, became the second director of IMT in November 2012.

On February 8, 2008 FLAFR signed a Framework Convention with IMT to support it's mission by providing grants of property, goods and services, and capital on a perpetual basis. This is in accordance with FLAFR’s statutory commitment to supporting the development and growth of IMT and consistent with the participation of FLAFR in the governance of the school via the Executive Council.

On April 22, 2011 the Executive Council approved the new statute of IMT to incorporate the changes introduced by the so-called “Gelmini Law” (L. 240 of December 30, 2010).

The interest of the city of Lucca in establishing a university dates back to 1300, as evidenced by documents showing the first attempts to establish centers of higher education of various natures or scope. In 1369 Emperor Charles IV gave official dispensation to the newly established Republic of Lucca to set up a Studium generale in the city. In 1387 this concession was further confirmed by Pope Urban VI. During the last century of the Republic of Lucca (1372-1805) there were university courses in logic, philosophy, ethics, surgery and anatomy, obstetrics, and canonical institutions and law, culminating in the establishment of the University of Lucca in 1802. The university was then abolished with the advent of the Principality of Elisa Bonaparte, and reformed during the Dukedom of Maria Luisa of Bourbon. In 1819 the Duchess of Lucca established the "Real Liceo" (Royal School), which was authorized to grant university degrees. The course of study at the Royal School was based largely on scientific topics, with tuition free to students, awarding scholarships to exceptional students and providing incentives for mobility between universities. The history of the Royal School was interrupted on October 22, 1849, following the reversion of the Duchy of Lucca to the Grand Duchy of Tuscany in 1847, and disappearing for good in 1867.

IMT School for Advanced Studies Lucca is the natural outcome of the right, enshrined in the fourteenth century and realized, even if only for a few decades, in the nineteenth century, for Lucca to be home to an active and independent academic institution.