In the area where is now located the Agostino Gemelli University Policlinic a villa or a farm should have existed, as during the refurbishment of an adjoining plot of land tufa and travertine blocks have been found.

After the fall of the Roman Empire, the area was used for cultivation and was largely uninhabited, forming part of the vast Agro Romano, with scattered huts and buildings.

In the Middle Age, the area was comprised within the vast estate called Casalia or Casalia Turris Vetulae (in Latin, Farmhouses or Farmhouses of the Old Tower), a large property owned by St. Peter's Basilica that included a number of adjacent neighborhoods, like Mimmoli, Sant'Agata, Palmarola, Mazzalupo, Sant'Andrea, Casal del Marmo and Pedica della Marinetta.

While the toponym Torrevecchia can be dated back to 1390, the name Primavalle appears for the first time in a map intended for hunters, drawn in 1547 by Eufrosino Della Volpaia.

In the same years, restoring and readjusting an old abandoned farmhouse, the nuns of the Congregation of the Poor Daughters of San Giuseppe Calasanzio established the Oasi di Primavalle, a social facility addressed to orphans and inmates' children, that later became a school.

The majority of the streets and squares of Primavalle is named after religious figures, like popes and cardinals, and after psychiatrists and physicians, revealing the closeness of the borough both to the Vatican City, to the south-east, and to Santa Maria della Pietà, a former mental hospital, to the north.