The whole building complex is built on the remains of the Odeon of Domitian: it is from there that the monolithic column, found in 1938 and erected in 1950,[1] comes from, placed in the centre of the small square, singularly quiet although it is immediately behind Piazza Navona.

Damaged by the Lansquenets during the Sack of Rome in 1527, the palace was partially rebuilt after 1532 by Giovanni Mangone,[2] a pupil of Antonio da Sangallo il Giovane.

The Palazzo Massimo istoriato, briefly Palazzo istoriato, obtained its name because it was decorated with frescoes with stories from antiquity, along the entire façade, probably by Daniele da Volterra in the 16th century, to celebrate the wedding of Angelo Massimo, who commissioned the reconstruction of the palace, with Antonietta Planca Incoronati.

One must bear in mind, when observing this architectural ensemble and evaluating its apparent eccentricity, that the layout of Corso Vittorio Emanuele – on which today stands Palazzo Massimo alle Colonne – and that of Corso Rinascimento were built after the unification of Italy, demolishing much of the area's medieval and Renaissance urban fabric, and profoundly altering its architectural barycentres.

The ground floor may have housed one of Rome's first typographies, opened by two German printers, Conrad Schweynheym and Arnold Pannartz.