The earliest records mention Thibaud I, Count of Blois, in the 10th Century. He founded a family that remained in power until 1230. It was at that time that the first stone castle surrounded by a bastion was erected. Of the many medieval remains, the best preserved is a tower on a terrace overlooking the Loire. In 1429, Joan of Arc went to Blois to seek the blessing of the Archbishop of Reims before embarking on her campaign against the English in Orleans. Prince Louis of Orleans, the son of King Charles V, lived in the castle for 25 years with a small court. His grandson, King Louis XII, decided to move to Blois, making it a royal town and capital of the kingdom.

With its four wings in different styles surrounding an inner court, the royal castle of Blois is a remarkable illustration of the development of French architecture from the 13th to the 17th Century. King Louis XII transformed the somber medieval fortress into a lavish and luminous castle. The wing he built in red brick and gray stone stands out with its Gothic exuberance. The king's equestrian statue adorns the façade above the entrance. Louis XII also had a Renaissance garden built; unfortunately, it was destroyed in 1890.

His successor and son-in-law, Francis I, built a new wing from 1515 to 1524. It is very different in style, with a marked Italian influence. The most prominent feature of the Francis I wing, a masterpiece of the French Renaissance, is the magnificent spiral staircase with three floors of balconies opening to the central court, and with fine sculptural decoration. The king's emblem, the salamander, can be seen sculptured in a dozen places on the façade. Francis I put together one of the largest libraries of his time in the castle. However, after the death of his wife, Queen Claude, he spent little time at Blois and had the library moved to the Fontainebleau Castle where it served as the basis for the National Library.

In 1588 King Henri III called a meeting of the Estates General in Blois and used the opportunity to have his greatest enemy, Henri of Guise, executed. The Queen Mother, Catherine de Medici, one of the most influential and power-loving women in French history, also died at the castle of Blois in 1589. The 'chamber of secrets' where she reportedly kept her poisons is exposed to visitors. In fact, it has never been proved that the cabinets were used for this purpose but that would not stop the flow of curious tourists.

The Wing of Gaston d'Orleans that closed the courtyard was built between 1635 and 1638 for the brother of Louis XIII. The architect, Francois Mansart, had a much grander plan for a building with four wings that never materialized. What was built, however, is a masterpiece of the Classical style, with three tiers of columns:  Doric, Ionic and Corinthian.

The castle was sacked during the French Revolution and fell into disrepair until Louis-Philippe ordered its restoration in 1841, and the castle was transformed into a museum. Since 1850, the apartments of Louis XII house a Museum of Fine Arts: a rich collection of paintings, sculptures and decorative arts from the 16th to the 19th century, and an impressive tapestry gallery.

Blois suffered heavy bombing during World War II and was meticulously restored by the architect Nicod.