In 1366, a nobleman Bernard of Szynwałd received permission from Casimir III to establish a settlement in the fields.

In 1384, Radymno was presented to the Bishops of Przemyśl, and in 1431 King Władysław II Jagiełło gave town charter to the village.

Due to its location by the San, and along a busy merchant route, Radymno was an important trade and market center.

To protect it from further raids, Radymno was fortified in 1625, but in 1656 it was captured by Swedes, and in 1657 by Transilvanians during the Swedish invasion of Poland.

Swedish wars left Radymno in ruins, and the town for many years did not recover from widespread destruction.

In the second half of the 18th century, before the Partitions of Poland, the population of Radymno was 1200, with 154 houses, three churches, hospital, parish school, two brickyards, and a residence of the Bishops of Przemyśl.

[3] As a result of the First Partition of Poland (Treaty of St-Petersburg dated 5 July 1772), Radymno was annexed by the Habsburg monarchy.

[6] On September 10, 1939, during the Invasion of Poland, which started World War II, German 4th Light Division crossed the San here, after a very light resistance and barely any battle with Polish Army's Jarosław Group under Colonel Jan Wójcik, who just escaped to the East as quickly as he could leaving Poland to defend itself.

Radymno fell under German occupation, and the Einsatzgruppe I entered the town to commit various atrocities against the populace.

[7] Officers of the local Polish military unit were among the victims of the large Katyn massacre, which was carried out by the Russians in April–May 1940.

[8] During the war, groups of the Organization of Ukrainian Nationalists, which operated in the area, murdered 59 Poles, including 29 killed in the village of Michałówka.

[9] The story of the Jewish residents of Radymno is documented in Dov Hister book The Power of Survival.

Radymno was captured by the Red Army on July 26, 1944, after heavy fighting with German armoured units, and afterwards it was restored to Poland.