The site on the Piazza Barberini in Rome's Rione Trevi had formerly been occupied by a garden-vineyard of the Sforza family, in which a palazzetto had been built in 1549.

The sloping site had passed from one cardinal to another during the sixteenth century, with no project fully getting off the ground.

When Cardinal Alessandro Sforza met financial hardships, the still semi-urban site had been purchased in 1625 by Maffeo Barberini, of the Barberini family, who had then taken the papal throne as Pope Urban VIII.

Three great architects work to create the Palazzo Barberini, each contributing his own style and character to the building.

Carlo Maderno, then at work extending the nave of St. Peter's, had been commissioned to enclose the Villa Sforza within a vast Renaissance block along the lines of Palazzo Farnese; however, the design has quickly evolved into a precedent-setting combination of an urban seat of princely power combined with a garden front that has the nature of a suburban villa with a semi-enclosed garden.

Maderno had begun in 1627, assisted by his nephew Francesco Borromini.

When Maderno died in 1629, Borromini had been passed over and the commission awarded to Bernini, a young prodigy at this time better known as a sculptor.

Borromini had stayed on regardless and the two architects had worked together, albeit briefly, on this project and at the Palazzo Spada.