In 1474, Lublin Voivodeship was created out of Sandomierz's eastern part, which included the Radomyśl area.

Radomyśl itself was founded as a private village in 1556 by local nobleman Jakub Sienienski.

Two years later, King Zygmunt August granted it a town charter (Magdeburg rights), and in 1584, King Stefan Batory gave permission for an annual fair and weekly markets, organized on each Monday.

In the 1772 First Partition of Poland Radomyśl was annexed by the Habsburg monarchy, becoming part of the Galicia and Lodomeria crownland.

During the Nazi occupation of Poland in World War II it was administered as part of the Lublin District of the General Government.