The town was first mentioned in 504 as Ambatia, when on the isle of Saint-Jean (now Île d'Or), Clovis, king of the Franks, met Alaric II, king of the Visigoths, to make a short-lived pact. In the 11th century Fulk III Nerra, count of Anjou, took the town from the count of Blois and built a high, square stone keep, from which the present château emerged. Thrusting up from a rock above the river, the château has a three-story facade flanked by two enormous squat towers. It was a favourite residence of French monarchs from the mid-15th century to the 17th century. Charles VIII, who was born and died there, brought artists from Italy to embellish the château.

Huguenot efforts to remove Francis II from the influence of the House of Guise were exposed in 1560 as the Conspiracy of Amboise (Amboise, Conspiracy of), and subsequently Protestant corpses hung from the balcony of the king's house, a Gothic portion of the château. Nevertheless, the Édict d'Amboise (1563) granted freedom of worship to Protestant nobility and gentry. From the time of Henry IV, the château was often used as a prison, and Abdelkader, the Algerian national leader, was confined there (1848–52). In 1872, after private owners had razed portions of the château, the National Assembly voted its return to the Orléans family.

In the town itself the 16th-century town hall is a museum. The Porte de l'Horloge is a 15th-century gateway with a carillon. To the southeast is Le Clos-Lucé, formerly the castle of Cloux, where Leonardo da Vinci died; it is now a museum. Immediately south is the seven-tiered Pagoda of Chanteloup, a piece of 18th-century chinoiserie. The local economy is diversified. Industrial development has extended there from Paris and includes the manufacture of precision instruments, pharmaceuticals, and vehicle components. Amboise is also the centre of the local winemaking industry and is an important tourist destination. Pop. (1999) 11,457; (2005 est.) 12,400.