The town has characteristics of medieval village in the shape of "S" and is enclosed within three rings of walls, all built to the fourteenth century.

Of Etruscan origin and founded, according to legend by Porsenna, Lucumone from Chiusi; some documents found in the Fortress, dates the existence already in IV-III century BC. In Roman times it was the seat of an army built to defend the consular roads. It was evangelized by St. Donatus, bishop of Arezzo in the fourth century.

The site of the Church of the Madonna di San Biagio, there was the Holy Mother Church in Castle Pulliciano, so in a document of 715 in Lombard times experienced its first development; Infact, in some deeds of the Archive of the Abbey of SS. Salvatore sull'Amiata, are documents including one 806 and the witnesses, all of Montepulciano, were priests, clerics, a doctor and a goldsmith, a sign of a high level of civilization and culture.

In the twelfth century, the Republic of Siena wanting to subdue Montepulciano, free and rich, began a series of wars, that Poliziani faced with the help of Perugia and Orvieto, but more assiduously and with mixed results, with the support Florence.

At the beginning of the thirteenth century, the vitality of the city, promoted by merchant class, manufacturing and agriculture, began to attract the sights of Florence and Siena.

The fourteenth century was marked by strong contention for power between the families more; relative stability came under the Family Of Sheep, divided among themselves in supporting Florence, Siena and Perugia, became Lords of Valiano and tyrants of Montepulciano.

In 1390 Montepulciano firmly allied with Florence, which was anxious to have a strategic stronghold south of Siena.

Since the beginning of the fifteenth century to the mid-sixteenth century, Montepulciano had its golden age, marked by political stability, cultural prestige, artistic flowering.

The fifteenth century was the era of the humanist Bartolomeo Aragazzi, apostolic secretary to Pope Martin V and the great poet Angelo Poliziano. Exceptional building fervor mark the sixteenth century architects such as Antonio da Sangallo the Elder, Jacopo Barozzi Vignola said, Baldassarre Peruzzi, Ippolito Scalza erected sumptuous patrician houses, splendid churches and different points of the city center were embellished.

In this period he lived Cardinal Marcello Cervini, who sat on the papal throne for just 28 days with the name of Marcellus II.

In 1511, the Poliziani, ended the final peace with the Florentines, engraved on the door and on the lintel of the boardroom the following inscription: Recuperatio Libertatis, AD 1511.

Since 1559, with the submission of the Medici principality Siena, Montepulciano lost part of the strategic and political past, but kept the prestige. They settled in Montepulciano historic families of the Nobles of Montepulciano, Tarugi, Contucci, Bellarmine, Ricci, Cervini, Benci, Cini, Cocconi and several others which gave great men of the Church, in letters, arts and weapons: a supreme pontiff, many cardinals, dozens of bishops, prelates distinguished in large number and a large amount of men who were excellent in many disciplines. One of his most loyal sons, Cardinal Giovanni Ricci, in 1561, obtained from Pope Pius IV, with the consent of the Grand Duke, who was decorated Montepulciano of the episcopal and the title of the city. Montepulciano got so the elevation to bishop's seat and performed the subsequent demolition of the old church to build the impressive cathedral (1594) designed by Ippolito Scalza and according to the principles of the Counter Reformation, which was one of the fathers emeritus Cardinal poliziano Robert Bellarmine.