The original core of the palace dates back to the 15th century, when it was the residence of the Benzoni family. Sold to Cardinal Ludovico Ludovisi in 1622, it was completely remodelled between 1620 and 1623 to a design by Maderno (1556-1629). After passing to the Colonna family, it was purchased in the mid-seventeenth century by Cardinal Fabio Chigi, who commissioned Gian Lorenzo Bernini (1598-1629) to design the façade. This corresponds to the left side delimited by the first eight pilasters, and has a large portal framed by two columns supporting a balcony with balustrades; on the sides are architraved windows with grilles and a sill supported by corbels. On the first floor are windows with alternating triangular and centred gables, while on the second floor the windows are architraved.
The windows on the first and second floors are punctuated by pilasters with composite capitals. Above them is a wide cornice with corbels and a high balustrade.
Bernini's scheme of the palace was a model for Baroque architecture, followed in Italy and abroad. In 1745, Baldassarre Odescalchi, the new owner of the palace, commissioned Nicolò Salvi (1697-1751) and Luigi Vanvitelli (1700-1773) to enlarge the building; the façade was thus doubled according to the previous Bernini model, adding as many windows and a second portal identical to the first.
This intervention profoundly altered the proportions of the original building designed by Bernini. In 1887 the façade, damaged by a fire, was restored, while the one facing Via del Corso was entirely rebuilt by the architect Raffaele Ojetti (1845-1924), in imitation of 15th century Florentine palaces, with an ashlar surface, a double floor with mullioned windows and a very protruding cornice. The interior of the palace has a rectangular arched courtyard with Doric pilasters and columns, dating back to Maderno's original design; on the first floor are windows set in arches and marked by double pilasters. At the end of the courtyard is a fountain with two dolphins and an eagle within a shell chalice, surmounted by the Odescalchi coat of arms. Inside the palace is "The Conversion of St. Paul" by Caravaggio, a work on wood that can probably be identified with the first version of the work commissioned in 1600 by Monsignor Tiberio Cerasi for his chapel, and then replaced with the painting currently in S. Maria del Popolo. It is one of the few works by Caravaggio belonging to a private collection