Dating back as far as the eleventh century, the building was substantially remodelled in the late sixteenth and early seventeenth century. The religious foundation here survived until its suppression in 1810, after which the building became a school: the Imperial Regio Ginnasio. In 1868 it became the premises of the Prefecture and the official residence of the Prefect.
Its wealth of architectural beauty includes: the main Council Chamber, the monumental entrance staircase, and even the gas and air-raid shelters constructed here during the war.
The Council Chamber was decorated in 1877 by Carlo Matscheg, an ornamentalist from Belluno, and Giulio Carlini, a painter from Venice. The most significant piece of refurbishment carried out here during the nineteenth century, the work included the decoration of the drum with a sequence of city crests and tondi containing figures from the history of Padua. Between these are allegorical depictions of Agriculture, Industry, Education, Commerce and the rivers Brenta and Bacchiglione. In the early years of the twentieth century Palazzo Santo Stefano was modified in layout and appearance, becoming what one sees nowadays. It was the architect Angelo Pisani who installed the Monumental Staircase in 1925, an imposing addition that defines the character of the building. In 1934 a gas shelter for 70 people was created, with a pedal-operated electrical ventilation system. Ten years later the Padua company of Zoccarato and Grassetto created a tubular air raid shelter and another shelter for the National Union of Air Protection in the garden of the Prefecture.Within the cloister of the old monastery, a total of four air-raid shelters have been identified, designed to provide protection for the students of a nearby high school, Liceo Tito Livio.