Traces of prehistoric settlements were unearthed (arrowheads) in peat-bogs. Recent finds have revealed Roman artifacts. During the Christian era, Padenghe was under the authority of the Parish Church of Desenzano del Garda, and the first church, San Cassiano, was built near the village on the lakefront. This first village was abandoned due to Hungarian incursions between the 9th and 10th centuries. The population fled to the hills, where a castle was built. In 1154 Padenghe was mentioned in the document with which Frederick Barbarossa, after the Roncaglia Diet, granted Theobald, the Bishop of Verona, all rights on several territories of Brescia.

During the Middle Ages, the castle of Padenghe served as the Ghibellina fortress and was the bone of contention between the cities of Brescia and Verona. In 1330 Padenghe was conquered by the Scaliger dynasty, which was ousted by John of Bohemia, the son of Emperor Henry VII. In 1362, Cansignorio of the Scaliger family took over the castle once again, but lost it two years later. At the end of the 14th century, the villages on the lake requested and obtained independence from the Visconti dynasty, and each town established its own statutes.

In 1414 Pandolfo Malatesta, who was the Lord of Brescia at the beginning of the century, handed over the Drugolo Castle (now in the Lonato area) to Padenghe. This castle had been taken from and later returned to the Vimercati family to punish their rebellion. After the Lodi Pact (1454), the Venice Republic kept a garrison in the Padenghe castle.

Maccheronic poet Teofilo Folengo, who at the beginning of the 16th century stayed at the Maguzzano Convent, said that the people of Padenghe were "superb". During their dominion, the French must have been intimidated by the citizens if in 1509 Governor Leonino Bibbia ordered the castle to be demolished, an act that was prevented through the intervention of Cardinal D'Amboise. In 1513 soldiers from the German Empire, who were based in Verona, pillaged and sacked the lake towns around Desenzano del Garda that formed the "Quadra di Campagna". These villages requested independence from Salò, but were denied this freedom.

Near the end of the 16th century the area was often at the mercy of ruthless bandits, including Giacomazzo from Padenghe, whose real name was Giacomo Dainese. The artist Andrea Giovanni Bertanza, who was born in Padenghe, was inspired by Palma il Giovane and Veronese; he worked in the Valtenesi area and on the lake Riviera at the end of the 16th century. Another person of note was the Jesuit Giambattista Rodella (1724-1794), a friend of Mazzucchelli, in whose home he lived for 22 years. He co-authored the "Dictionary of Italian Authors", wrote several works and also translated. The Zuliani brothers of Padenghe on lake Garda became famous at the turn of the 19th century: both Andrea, a distinguished lawyer, and Francesco, a well-known physician, were professors.

During the Risorgimento, the volunteers of Tito Speri captured Austrian general Schonhals on March 28, 1848, who was fleeing from Brescia that had risen in revolt. Between 1928 and 1947 the villages of Moniga del Garda and Soiano joined the Padenghe municipality and subsequently became autonomous.

The name of the town Padenghe derives from the family name Padus. Cocchetti hypothesizes that the name comes from the Ligurian word "podinco" (bottomless). The name "Patengulis" existed in the area after the year 1000.