Built starting in 1413 by Paolo Guinigi, Lord of Lucca, the villa, an imposing structure in brick, was surrounded by a great garden abounding in vegetables, fruit trees, birdcages and fountains; originally a "country residence" outside the city walls, it was later encapsulated within the new circle of walls. In 1430 the villa became the property of the Republic of Lucca. After various vicissitudes in which its appearance was altered, in 1924 it became the site of a Civic Museum. In the years following World War II, it was restored to its original form and, in 1968, the Civic Museum became a National Museum. The Museum aims to illustrate the historical-artistic development of Lucca and its countryside. The main collections include, in fact, archaeological material with prehistoric, Etruscan and Roman remains, a collection of sculptures and paintings dating from the Middle Ages to the Baroque period and a collection of ecclesiastical furnishings and fabrics.

As regards scientific aspects, the Museum possesses apparatus coming from the Hospital of San Luca (on loan to the Pinacoteca Nazionale of Palazzo Mansi) and some eighteenth-nineteenth century measurement instruments. It also has a collection of instruments for weighing and measuring lengths in use in the territory of Lucca during the 19th century (at present, these objects are stored in the attic of Villa Guinigi and are not on display).