The first known mention of the Palazzo Pesaro occurs on 9 February 1372 in a document from the Signori della Notte to the Criminal.

The present palazzo dates from the mid-fifteenth century: its façade was constructed in the years between 1450 and 1460 and is characterised by its clustering of gothic quadriform windows with elegantly carved balconies (below).

The ceiling of the main room on the piano nobile with its frieze of alternating consoles and military spoils (below) was constructed at the end of the sixteenth century.

In 1625, the noblewoman Pesarina Pesaro was married to the rich citizen Bonifazio Papafava (who, on 22 December 1652, was admitted into the ranks of the Venetian patriciate), and since then the palace has been known as the Palazzo Pesaro-Papafava. The palace eventually became the property of the Papafava dynasty.