Founded in 1889 and inaugurated in 1890, the museum's first aim was to collect and exhibit archaeologic materials unearthed during the excavations after the union of Rome with the Kingdom of Italy.

Its seat was established in the charterhouse designed and realised in the 16th century by Michelangelo within the Baths of Diocletian, which currently houses the epigraphic and the protohistoric sections of the modern museum, while the main collection of ancient art was moved to the nearby Palazzo Massimo alle Terme, acquired by the Italian state in 1981.

The present building was commissioned by Prince Massimiliano Massimo, so as to give a seat to the Jesuit Roman College, originally within the convent of the Church of St. Ignatius of Loyola at Campus Martius.

In 1981, when the palace was lying in a state of neglect and disrepair, the Italian Government acquired it for 19 billion lira and granted it to the National Roman Museum.

One room is devoted to the mummy that was found in 1964 on the Via Cassia, inside a richly decorated sarcophagus with several artefacts in amber and pieces of jewellery also on display.

The frescoes, discovered in 1863 and dating back to the 1st century BC, show a luscious garden with ornamental plants and pomegranate trees.

Among the coins on exhibit are Theodoric’s medallion, the four ducats of Pope Paul II with the navicella of Saint Peter, and the silver piastre of the Papal State with views of the city of Rome.

When the Riario family began to decline after the death of Pope Sixtus IV, the palazzo was sold to Cardinal Francesco Soderini of Volterra, who commissioned further refinements from the architects Sangallo the Elder and Baldassare Peruzzi.

When the Soderini family fell on hard times, he in turn sold it in 1568 to the Austrian-born cardinal Mark Sittich von Hohenems Altemps, the son of the sister of Pope Pius IV.

Roberto's granddaughter Maria Cristina d'Altemps married Ippolito Lante Montefeltro della Rovere, Duke of Bomarzo.

In 1981, digging on a derelict site in the Campus Martius between the churches of Santa Caterina dei Funari and Santo Stanislao dei Polacchi, Daniel Manacorda and his team discovered the colonnaded quadriporticus of the Theatre of Lucius Cornelius Balbus, the nearby statio annonae and evidence of later, medieval occupation of the site.

These are presented in this branch of the museum, inaugurated in 2001, which houses the archaeological remains and finds from that dig (including a stucco arch from the porticus).

As well as showing the remains from the site itself, this section also tells of the Monastero di Santa Maria Domine Rose (begun nearby in the 8th century), of medieval merchants' and craftsmen's homes, of the Conservatorio di Santa Caterina dei Funari (built in the mid-16th century by Ignatius of Loyola to house the daughters of Roman prostitutes) and of the Botteghe Oscure.

With a side length of 40 meters (half the size of Michelangelo's Cloister) it today features exhibits on the Arval Brethren and on the Secular Games.