Pyzdry is one of the oldest town of the province, as in 1257 it was mentioned as a location governed by a vogt, which means that a well-established urban center must have already existed here.

After the successful Greater Poland uprising of 1806, it was regained by Poles, and included within the newly established, however short-lived Duchy of Warsaw.

Following the duchy's dissolution in 1815, it became part of Russian-controlled Congress Poland, in which it remained until World War I, and was the westernmost point of the Russian Empire.

Following the joint German-Soviet invasion of Poland, which started World War II in September 1939, the town was occupied by Germany until 1945.

The town has several points of interest: Among people born here are Mikołaj of Pyzdry (rector of Jagiellonian University), writer Stefan Otwinowski and film director Ewa Petelska.