The origins of Grosseto trace back to the High Middle Ages. It is first mentioned in 803 as a fief of the Counts Aldobrandeschi, in a document stating the assignment of the church of St. George to Ildebrando degli Aldobrandeschi, whose successor where counts of the Grossetana Mark until the end of the 12th century. It grew in importance with years, owing to the decay of Rusellæ and Vetulonia. Grosseto was one of the principal Etruscan cities. In 1137 the city was sieged by German troops led by duke Henry X of Bavaria, send by the emperor Lothair III to reinstate his authority over the Aldobrandeschi. The year later the bishopric of Roselle was transferred in Grosseto.
In 1151 the citizens swore loyalty to Siena. When in 1222 the Aldobrandeschi gave the Grossetani the right to have a podestà of their own, together with three councellors and the consuls. In 1244, the city passed again to Siena, together with all the Aldobrandeschi's imperial privileges as the Sienese captured it and were legally invested with it by the imperial vicar; thus Grosseto shared the fortuned of Siena. It became an important stronghold, and the fortress (rocca), the walls and bastions are still to be seen. In 1266 and in 1355, it sought freedom from the overlordship of Siena, but in vain. While Guelph and Ghibelline parties struggled within the city, Umberto and Aldobrandino Aldobrandeschi tried to regain to their family Grosseto. The Senese armies were however victorious, and in 1259 they named a podestà from their city. But Grosseto freed and the year later fought alongside with Florence in the Battle of Montaperti. The following decades saw Grosseto again occupied, ravaged, excommunicated by Pope Clement IV, again free under a republic led by Maria Scozia Tolomei, sieged by emperor Louis IV (1328) and by the antipope Nicholas V in 1336, until it definitively submitted to the most powerful Siena.
The pestilence of 1348 struck hard against Grosseto, whose population in 1369 had reduced to some a hundred of familiar nuclei. Its territory, moreover, was frequently ravaged, as in 1447 by Alfons V of Sicily and in 1455 by Jacopo Piccinino.
The Sienese rule ended in 1559, when Charles V handed over the whole duchy to Cosimo I de Medici, first Grand Duke of Tuscany. In 1574 the construction of a line of walls was begun, which is still today well preserved, while the surrounding plain was dried. Grosseto, however, remained a second rate town, with only 700 inhabitants at the beginning of the 18th century.
Under the rule of the House of Lorraine, Grosseto reflourished. It was given the title of capital of the new Maremma province.