Instituted as a subordinate Section of the Siena State Archives in 1958, it became a State Archive in 1963. Local documentation on the feudal and city-state period, conserved in the Episcopate Archive, was lost due to bombing in 1943 and due to floods in 1944 and 1966. The oldest papers of the Grosseto Province are kept in the Siena State Archive. The territory of Grosseto was, in fact, subject to the Sienese magistrature from the 13th century to 1557, the year when Siena became a part of the State of Tuscany. In 1766, with the separation of the Lower Sienese Province from Siena, ordered by Grand Duke Peter Leopold of Lorraine, Grosseto became an independent province. The Grosseto documentation finds completion in the papers conserved in the Diplomatic Archives of the Florence State Archive.

Especially interesting, from the technical-scientific viewpoint, is the historical documentation on the draining of the swamps around Grosseto under the Lorraines, for which the Tuscan government decided to institute, through a decree of 1828, a "hydraulic-economic commission for the physical reduction of the Maremma", which was to develop into the Land Reclamation Department. No less interesting, however, are the collections of the Grosseto Misericordia Hospital (1770-1888) and of the Orbetello Hospital.