The Palazzo Salimbeni was built as a fortress (Rocca) by the then powerful Sienese Salimbeni family in the 12th century. In the 13th century, after two popular uprisings initiated by the Salimbeni (1264 and 1268), the Rocca was destroyed, but immediately afterwards rebuilt by the Salimbeni. Due to several attempts to seize power in the city and their Guelph sentiments, the family was expelled from the city in 1419 and their property, including the Palazzo Salimbeni, was confiscated by the city and the Republic of Siena.
The city council first installed the Gabelle for salt and grain here. When the Monte dei Paschi bank was founded in 1472 (still known as Monte Pio), it was also allocated rooms in the Palazzo.
In 1866, the Palazzo Salimbeni was purchased in its entirety for 60,743 lire by Monte dei Paschi, which had the building restored from 1883 to 1887 by the architect Giuseppe Partini.
The façade on Piazza Salimbeni was already altered in 1871 and from 1877 to 1879, and the entrance area was enlarged. Further renovation work was decided in 1959 and carried out from 1963 to 1972 by Pierluigi Spadolini (* April 15, 1922 in Florence; † June 8, 2000 ibid.). The so-called Intervento di Spadolini included the condition of restoration while preserving the original structures as much as possible. The only major changes were the removal of the Cortile della Dogana, where the wooden staircase now called Scala Spadolini was built, and the transformation of the former church of San Donato inside into an assembly room.