The museum is located in the Palazzo del Marzocco, a 16th century structure which joined two pre-existing tower houses. The Marzocco is referred to in the name is a stone lion at the right corner of the facade which was placed there by the Florentines in 1526 as a symbol of the sovereignty of the Florentine Republic which ruled here from 1388. The museum opened in 2000 and is organized under nine themes which relate to local history.
The collection includes a number of notable works including important prehistorical and Roman artefacts, and relics of important wars from the Middle Ages and Renaissance. An entire section is dedicated to the Battle of Anghiari and the painting of this subject by Leonardo da Vinci.
The museum is partially accessible for wheelchair users. The prehistoric section includes a touch tour for people who are blind are partially sighted and labels in braille.