Until the 15th century this street was divided into smaller segments each named either for the type of business operated on that section or the family who owned the buildings lining it: Via dei Cacioli (cheese sellers), Via de' Banderai (the flag makers), Via de' Bonagiusi (a mercantile family which still owns the palazzo on the corner of Via Condotta), Via dei Brigliai (rein makers), the Corso degli Adimari, and the Corso dei Pittori (painters).
The church of Orsanmichele rises on the same spot where an earlier, 8th century convent was located with a large vegetable garden (orto). This gave rise to the church's name—San Michele in Orto—which has been shortened in the years to Orsanmichele. In the mid-13th century the building was transformed into a grain market. In 1304 the building suffered significant damage in a fire and was rebuilt over the next century on the current, rectangular floor plan with two storeys. The niches on the exterior of the building hold copies of the 14 statues of patron saints commissioned by the city's major guilds, with works by Donatello, Verrocchio, Ghiberti, Giambologna and Nanni di Banco. The originals can be seen at the museum inside.
The Church of Saint Carlo dei Lombardi, on the opposite side of the street, was begun in 1349 by the Signoria, the ruling body of the city and dedicated to Saint Carlo. It passed into the hands of the brotherhood of the “Lombard Nation” in 1616 and since then has been known as Saint Carlo “dei Lombardi.” This street was also the site of Florence's first emporium, the Bazar Bonajuti which opened in the 1800s on the site where the Coin store is found today. The emporium moved at the beginning of the 20th century, but remained open until 1988.