Leszno was first mentioned in historical documents in 1393. The settlement was then the property of Stefan z Karnina of Clan Wieniawa. The family adopted the surname of Leszczyński from the name of their estate according to the medieval custom of the Polish nobility.
In the early 16th century a community of Protestant Unity of the Brethren refugees from Bohemia settled in Leszno invited by the Leszczyński family, who were since 1473 imperial counts and had converted to Calvinism. The arrival of the Bohemian Protestants as well as weavers from nearby Silesia helped the settlement to grow and made it possible to became a town in 1547 by a privilege given by King Sigismund I the Old. Leszno was also the biggest printing center in Greater Poland thanks to the activity of the Protestant community, whose number increased because of inflow of German refugees from Silesia during the Thirty Years War. At the time it already had a Gymnasium school led for a period by Jan Amos Komenský (known in English as Comenius), a Bohemian educator who was a bishop of the Unity of the Brethren. From 1638 to his death in 1647, Johann Heermann, a German-speaking poet, lived in Leszno. Between 1636 and 1639 the town became fortified and its area increased. The golden era of Leszno ended with a large fire in 1655. During the Great Northern War the town was burned again in 1707 by Russians and had a plague in 1709. The Leszczyński family owned the city until 1738 when king Stanisław Leszczyński sold it after he abdicated for the second time.