The château fell into decline from the second half of the 16th century and the majority of the interior buildings were later demolished, but some survived and have been restored, along with the outer defensive circuit of towers and walls.

While Conan was busy on Anjou's western border, Gelduin and Robert attempted to isolate the easternmost castles of Amboise and Loches by raiding the Saumurois and disrupting communications.

King Francis I was raised at Amboise, which belonged to his mother, Louise of Savoy, and during the first few years of his reign, the château reached the pinnacle of its glory.

After the French Revolution (1789–1799), the Chapel of St Florentin was in such a ruinous state that the engineer appointed by Napoleon decided that it was not worth preserving and had it demolished.

Nonetheless, based on some contemporaneous accounts, it is the collection of bones that were found to be whole and with an extraordinarily large skull that are supposed to be buried in the Chapel of Saint Hubert, where now a large floor-level marble stone bearing a metal medallion relief portrait of Leonardo da Vinci (based on the "Melzi's portrait") and the words LEONARDO DA VINCI seem indicative of his final resting place.

By the time it was finished, 1,200 Protestants were gibbetted, strung from the town walls, hung from the iron hooks that held pennants and tapestries on festive occasions and from the very balcony of the Logis du Roy.

At the beginning of the 17th century, the huge château was all but abandoned when the property passed into the hands of Gaston, Duke of Orléans, the brother of the Bourbon King Louis XIII.

After his death it returned to the Crown and was turned into a prison during the Fronde, and under Louis XIV it held disgraced minister Nicolas Fouquet and the duc de Lauzun.

Emperor Napoleon Bonaparte gifted Amboise to Roger Ducos who, after an engineering assessment, decided to destroy a large part of the castle in order to reduce its costs.

The captive Emir Abd Al-Qadir, who resisted the French colonisation of Algeria, and an entourage of family and retainers were transferred to Château d'Amboise in November 1848.

Amboise, a few years since, was a smiling, lively little town, and the castle was a pleasure residence of the last king; the gardens were delicious, the little chapter of St. Hubert a gem, restored in all its lustre, and the glory of artists and amateurs.

All is now changed: a gloom has fallen on the scene, the flowers are faded, the gates are closed, they pretty pavilions are shut-up; there are guards instead of gardeners, and a dreary prison frowns over the reflecting waters, which glide mournfully past the towers.Later that year, in October, President Louis-Napoléon Bonaparte visited Abd al-Qadir at Amboise to give him the news of his release.