It is located in the former Saint Ignatius Jesuit novitiate of the city's University district, and inside the same building that houses the Academy of Fine Arts.

According to 18th-century Italian art historian Luigi Crespi, it was cardinal Prospero Lambertini, who would later become Pope Benedict XIV, the one who planned a Gallery for altarpieces in the churches of the city.

The gallery's first nucleus of works came from the acquisition in 1762 by monsignor Francesco Zambeccari of eight early 15th-century altarpieces, salvaged from the demolition of Saint Mary Magdalene's church.

The Bolognese senate decided to merge the suppressed churches' and convents' paintings and Accademia delle Scienze's holdings into one single collection, gathering almost one thousand works, organized first at the former Convent of St Vitalis, then in 1802 at the former Jesuit novitiate of Saint Ignatius in the Borgo della Paglia, now called via delle Belle Arti 56, made by Alfonso Torreggiani in 1726 to house the newly created gallery of National Academy of Fine Arts.

In the late sixties under supervisor Cesare Gnudi and based on Leone Pancaldi's project, the Salone del Rinascimento was created to host the frescoes brought from the Sant'Apollonia di Mezzaratta church.