This street was known in ancient times as via Galgaria. It lies at the heart of the city, connecting the Campo with the Duomo and the old Santa Maria della Scala Hospital. One of the most interesting starting places is the alley Costarella dei Barbieri, where the Palio begins and ends. Historians say that this was the site of the ancient porta Salaria, where the Triventum marked how the city was to be divided into three medieval administrative districts – the Terzo di Camollia, Terzo S. Martino and the Terzo di Città. Due to the major developments of the Middle Ages only buildings constructed from the thirteenth century onwards have survived, even though the foundations of the street are ancient. Immediately on the left is the elegant Palazzo d'Elci, now headquarters of the local tourism promotion agency. This has a sweep of nineteenth-century steps and two paintings by Daniele Ricciarelli da Volterra on the first floor. After the entrance to the narrow Bargello chiasso and the distinctive view of the Torre del Mangia, is the dignified Palazzo Patrizi. This was the ancient and prestigious headquarters of the Accademia of the intronati – the dazed ones. The institute was founded in 1525 by erudite men in the inner circle of Enea Silvio Piccolomini, Pope Pius II. Their emblem is the pumpkin, a container for salt – ''sale in zucca'' or common sense – crossed with two pestles, above the entrance. The building's fourteenth-century layout was remodelled in the sixteenth century with the magnificent central hall decorated with figures and landscapes by Giorgio di Giovanni – a disciple of Beccafumi – stuccoes by Marcello Sparti and paintings by Flemish artist Bernardo Van Rantwyck (1583).

Continuing along this street we find the Marescotti palazzo, now called Palazzo Chigi Saracini and Palazzo delle Papesse (see below), followed by the prototype Sienese Gothic palazzo, Palazzo Marsili. This still has its brick structure and shows the neo-Gothic additions by the architect Partini (1870), a great advocate of a return to what he saw as architectural origins. On this building's façade is the Piccolomini coat-of-arms held by angels.