The lands were inhabited by the Baltic tribe Yotvingians. Due to the frequent raids and pillaging of Teutonic Order, Yotvingians abandoned the lands and Seirijai became a wilderness. From 1383 to 1398 Seirijai was in the State of the Teutonic Order. After the defeat of Teutonic Order in the Battle of Grunwald and the Treaty of Melno (1422), the land became populated again and started to grow economically. Since 16th century Serijai were known as a proprietary land of a ruler. King of Poland and Grand Duke of Lithuania Sigismund I the Old donated Seirijai to Jurgis Radvila, and later it became a possession of Radvila family. Jurgis Radvila built a Catholic church in 1537. Already in 1564 the church was given to Calvinists, since many in Radvila family converted to Calvinism. The tensions between Catholics and Calvinists lasted up to 1655 the Thirteen Years' War with Russia. Seirijai town was devastated and Calvinists retreated.