The Vasari Corridor was built in 5 months by order of Duke Cosimo I de' Medici in 1564, to the design of Giorgio Vasari. It was commissioned in connection with the marriage of Cosimo's son, Francesco, with Johanna of Austria. The idea of an enclosed passageway was motivated by the Grand Duke's desire to move freely between his residence and the government palace, when, like most monarchs of the period, he felt insecure in public, in his case especially because he had replaced the Republic of Florence. The meat market of Ponte Vecchio was moved to avoid its smell reaching into the passage, its place being taken by the goldsmith shops that still occupy the bridge. At the latter extremity, the corridor was forced to pass around the Mannelli's Tower, after the staunch opposition of that family to its destruction.

In the middle of Ponte Vecchio the corridor is characterized by a series of panoramic windows facing the Arno, in the direction of the Ponte Santa Trinita. These replaced the smaller windows of the original construction in 1939, by order ofBenito Mussolini. The larger windows were installed for an official visit to Florence by Adolf Hitler to give him a panoramic view of the river.

After the Ponte Vecchio the Corridor passes over the loggiato of the church of Santa Felicita; at that point it had a balcony, protected by a thick railing, looking into the interior of the church, in order to allow the Grand Duke's family to follow services without mixing with the populace.

In its Uffizi section the Vasari Corridor is used to exhibit the museum's famous collection of self-portraits.