Montagnana is built on the site of an ancient prehistoric settlement dating from the Neolithic and Bronze Ages. Later, the Romans made it a "castrum" fortified to defend the bridge over the Adige River, which was a major meeting point of the famous 'Via Emilia Altinate' that linked Modena and Altino.

The Latin name for Montignana - 'Motta Aeniana' - comes from the fact that the settlements were on some "motte" (little hills), while the term 'Aeniana' refers to the ancient Roman road called 'Annia', another name for the Via Emilia Altinate.

Between the ninth and tenth centuries the city began to take form around a castle, and by the twelfth century had become a fortified town contended by the great Lords of the time: the Marquis of Tuscany, the Obertenghi and Estes. Around the middle of the 12th century Montagnana became a Municipality.

The medieval history of Montagnana continues with its conquest by Ezzelino da Romano in the mid-13th century. The first set of reinforcements extending the defensive wall, which continued into the 14th century were completed around 1362 with the construction of the so-called 'Rocca degli Alberi'.

In the early 15th century Montagnana was ruled by Venice, which held the city until the Napoleonic age (1797). The Venetian period was a time of economic prosperity for the town, especially with the production of hemp and the work of the local mills.

The Pisani, Venetian nobles, embellished the city with a palace built by Palladio (1508-1580) and the Cathedral of Santa Maria Assunta was built in the early 16th century. Considerable building activity continued during the following centuries.

After the fall of Venice, Montagnana was ruled by the French and later the Austrians until 1866 when it entered the Kingdom of Italy.