On January 4, 1887, Pope Leo XIII issued a papal brief ("Quae diligenter") that formally commissioned the re-establishment of a residential college for the new Benedictine Confederation.

[2] Abbot Gaetano Bernardi began the search for suitable land and was approached by Count Allesandro Barbiellini Amidei who owned property on the western Aventine Hill which had contained the previous fortifications of a house for Pope Paul III.

In his July 26, 1890, circular letter, Abbot Bernardi wrote that "It is on the Aventine Hill on which our St. Odo (of Cluny), thanks to the generosity of Alberich from the family of the Counts of Tusculum, built a monastery and church in honor of Mary...." He further mentioned that Pope Gregory VII had spent his youth in a monastery there and recounted, "Of all the places in Rome what better placed could we have wished for!

"[3] The newly envisioned complex would allow for the housing of the residential college, a church, and the central offices of the Benedictine Confederation.

The entire "Sant'Anselmo" complex on the Aventine Hill was designed by Belgian Benedictine Abbot Hildebrand de Hemptinne and Fidelis von Stotzingen and built by Francesco Vespignani between 1892 and 1896 in a neo-romanesque style.

To honor the founding vision of Pope Leo XIII, a large sculpture of him was crafted in 1891 by Giuseppe Luchetti and is located in the interior sacristy of the church.

The mosaics are located above the two side altars, as well as above the main apse which depicts the jeweled cross between angels and Saints Benedict and Anselm.

Commandeur also completed the mosaic under the main altar covering the reliquary containing the relics of Saint Alexander of Rome.

In the entrance to the Sant'Anselmo complex, reached from the atrium, is a Roman Orpheus mosaic from a second-third century home that was found during construction.

Since 1962, the church has also been the starting point of the penitential procession presided over by the Pope on Ash Wednesday, and which ends at the basilica of Santa Sabina where the first stationary mass of Lent is celebrated.

[17] The Benedictine Confederation is a union of monastic congregations that nevertheless retain their own autonomy, established by Pope Leo XIII on July 12, 1893, in his brief "Summum semper".