The museum was founded in 1588 by the Grand Duke Ferdinando I, who established a workshop to produce the rare or precious stones for the decoration of the Chapel of Princes. In 1796, Pietro Leopoldo had the Opificio transferred to its present headquarters in Via degli Alfani.
The Opificio, whose workshops are now situated in Fortezza da Basso, still continues its tradition of executing and restoring mosaics made from pietra dura, Florentine commesso, sections and tesserae.