The school, situated in the ancient boarding school opened by the Jesuits in 1687, was instituted in 1856 as the Imperiale e Regio Liceo Aretino [Imperial and Royal Arezzo Secondary school]; in 1865 it was named for the poet Petrarch. Originally it consisted of classes in Grammar, Rhetoric, Philosophy, Higher Mathematics, Physics and Civil Law. The directors of the Secondary school was also responsible for directing the Technical Schools up until 1873 and the Intermediate School until 1892, when the latter, having separated from the Secondary school, became a "Communal, Officially Recognised and Compulsory" school. In 1923, subsequent to the school system reform promoted by Giovanni Gentile, the Intermediate School and Secondary school were reunited and the institute took the name of Regio Liceo-Ginnasio "Francesco Petrarca" ["Francesco Petrarca" Royal Intermediate School-Secondary School].

Along with a library, laboratories and a multimedia hall, the Secondary School has an important collection of scientific instruments, including nineteenth- and twentieth-century teaching apparatus for mechanics, electrostatics, electricity, astronomical geography, radio engineering and anatomy. Noteworthy among all are a Marconi receiver with choerer from 1910, Crookes tubes and Geissler tubes, a Gay-Lussac pump, an Italian armillary sphere, a planisphere and a celestial globe. The school also possesses a naturalist collection made up of minerals, insects, fossilised specimens, botanical and anatomical models used in teaching, as well as a zoological collection with both stuffed animals and specimens preserved in formalin.