Founded in 1564 to highlight the statue of Neptune to which it owes its name, the square was the result of the expansion of the existing space between Palazzo d'Accursio and Palazzo del Podestà through the demolition of a block of buildings. The statue of Neptune was built between 1563 and 1567 by the Flemish sculptor Jean de Boulogne, known as Giambologna, and by Tommaso Laureti, known as Il Siciliano. On one side of the square is the Sala Borsa, since 2001 the Multimedia Civic Library, on the other, next to Palazzo del Podestà, stands Palazzo Re Enzo.

The Basilica of San Petronio, dedicated to the city's patron saint, stands in Piazza Maggiore and is the largest and most important church in Bologna. Construction began in 1390 under the direction of Antonio di Vincenzo. In 1514 Arduino degli Arriguzzi proposed a new Latin cross model that would have exceeded the size of the church of San Pietro in Rome, but, according to legend, Pius IV blocked its construction by soliciting the works for the construction of the Archiginnasio. Famous is the Musical Chapel of San Petronio, the oldest musical institution in Bologna (1436), whose most prestigious symbol is a still functioning organ, which, built around 1470 by Lorenzo da Prato, is the oldest in the world still in use

A truly special itinerary is the one that takes you through the streets of the ancient market of Bologna, the Quadrilatero. This district already housed most of the city's artisan guilds since the Middle Ages and is today one of those most characteristic places in Bologna.

Piazza Santo Stefano is one of the symbolic places of Bologna, commonly considered a square, although it is actually a widening originating from Via Santo Stefano and leading to the homonymous complex, also known as "Seven Churches". Dominated by the Basilica of Santo Stefano, the square has the Berti house, Palazzo Isolani and Palazzo Bolognini Isolani on one side, and the sixteenth-century Palazzo Bolognini Amorini Salina on the other.

The sanctuary of the Madonna di San Luca (San Lócca in Bolognese) is a basilica dedicated to the Catholic Marian cult and stands on the Colle della Guardia, a partly wooded spur at 280 m a.s.l. south-west of the historic center of Bologna. It is an important sanctuary in the history of the city, since its origins a pilgrimage destination to venerate the icon of the Virgin and Child called "di San Luca". The sanctuary can be reached from Porta Saragozza through a long and characteristic arcaded road, which crosses via Saragozza with the monumental Arco del Meloncello (1732) and then climbs steeply up to the sanctuary.