The origin of Montepulciano dates back to a remote era; according to tradition it was founded by the Etruscan King Porsenna in the 6th century BC. Others have identified that on this mountain there once stood a place called "Arretium Fidens" and yet others identify the site with "Novum Clusium", spoken of by Pliny the Elder (23-79 AD).

Many Etruscan and Roman finds have been made in this district confirming its great antiquity.

The name of Montepulciano is not so ncient, and is perhaps unknown until the beginning of the 8th century, when it appears in a document dating 715 by King Liutprando (690 ca.-744).

Montepulciano in the Middle Ages

Before the 12th century the events around the town's history are unknown. Then we know that it was disputed between Siena and Florence; in fact, the Sienese claimed that the castle and territory of Montepulciano was included in their county. The growth of Montepulciano was especially important for the two powerful towns of Siena and Florence, which, through its ownership of the city, would have enabled them to gain control of the “Val di Chiana” and “Val  d'Orcia”.

The Florentines and Sienese clashed several times for possession of Montepulciano, and in 1232 Siena managed to take control of the city after having razed the walls. From this time on, and for the next three centuries, the city comes in the orbit of Siena or Florence, as it consolidated the presence of a strong middle class within the city, which based its wealth and power on trade.

Around the middle of the 13th century the city expanded towards the hill of St. Francis, with further growth in the 13th-14th centuries establishing the definitive urban plan.

From the 14th century the role of Montepulciano is clearly delineated - the trading activities benefited from a privileged location of the city on important trade routes, with local businesses based on a market that served as a trading point between farmers in the “Val d'Orcia” and “Val di Chiana”. But if the 14th century was a time in which the town flourished, it was also a time of lively conflicts among the dominant groups, until the establishment of the lordship of the Del Pecora Family, who ruled with varying fortunes until the submission of Montepulciano to Florence in 1390.

During the 15th century the effects of the Florentine dominion were prominent in the city, in the fields of politics, architecture and urban planning.The first major building operation was in the Piazza Grande by the Florentine architect Michelozzo Michelozzi (1396-1472), with the reorganization of the “Palazzo Comunale”.

After a final period of domination by Siena (from 1495 to 1511), Montepulciano experienced in the 16th century a process of renewal, with the presence of Antonio da San Gallo the Elder (1453-1534), who started the building of the Fort, built the church of the Madonna di S. Biagio and numerous mansions (Contucci, Cecconi, Cervini).

The embellishment of the city also involved other architects such as Baldassarre Peruzzi (1481-1536), Jacopo da Vignola (1507-1573) and Ippolito Scalza (1532-1617). The importance of the city was underlined by its appointment as an episcopal seat in 1561.

From 1609 to 1636 Montepulciano was under Ferdinand I de Medici (1549-1609) and his widow, Christina of Lorraine (1565-1637), and during this period many great religious buildings were built (completion of the Cathedral, the churches of Jesus, St. Lucia, St. Bernard, St. Joseph, and St. Lawrence).

Montepulciano in recent centuries

From the middle of the 18th century, coinciding with the program of the Dukes of Lorraine to rearrange the Chiana Valley, there has been a slow process of upgrading within the city, which had its most significant moment in the construction of the “ ‘Poliziano’ Theater” (1793-96).

The final arrangement of the functions of the city was the completion of the reclamation of the Chiana Valley, when the new plains road was completed connecting Arezzo, Foiano, Bettolle, and Chiusi in 1835.

Montepulciano in the 19th century became an important agricultural market and centre for processing agricultural products. In the last decades of the 19th century some interventions were implemented in the health standards such as the Public Slaughterhouses and the arrangement of the “Poggiofanti” Gardens (1866-75) outside of the "Porta al Prato" in the north of the city.

The early 20th century brought a shift in activities to the road outside Montepulciano, in the direction of Chiusi-Chianciano, which began a consequent transformation of the city and the old Town is now used for functions related to services, such as banks, insurance companies, local governments and other productive activities.