In 1659, under Louis XIV, the abbess Anne de Chaulnes obtained the necessary funds to construct the Royal Abbey. Royers de la Valfenière, an architect from Avignon, designed an imposing, Italian-inspired building composed of four wings around a cloister. Work was finished in 1685 under the direction of the abbess Antoinette de Chaulnes, Anne's sister.

Around thirty nuns, who were mostly of high aristocratic descent, lived there under the authority of the abbess. In 1730, the abbey was home to some sixty Benedictine nuns, and thirty-two were living there in 1792, when they were expelled. Decorated with beautiful pink marble columns, the private prayer chapel remains as a vestige of their living quarters. It now houses the Greek vase collection. In the 18th century, the abbey was among the wealthiest in France, in particular because of revenue obtained from store rentals on the ground level.

Founded in the 7th century, the church was rebuilt in the 12th century in the Romanesque style. The windows found in the interior passageway and the splendid porch date from this period. Side chapels were added in the 14th century. The current site was designed in the 18th century by the architect A. Degérando (active in Lyon from 1731 to 1773). He enlarged the choir, built the bell tower and decorated the arches and pilasters. Deconsecrated in 1907, the church was allotted to the museum.