Historical records do show Prienai and its surrounding land being mentioned as long ago as the Great Kingdom of Lithuania (the 14th century). Royal estates near Prienai, built along the banks of the Nemunas, guaranteed favorable conditions for trade while allowing a defensive position. This was important because Prienai’s centralized location saw many bands of intruders march through the area causing destructions to home and lives. Swedish army, French soldiers, Russian and German armies marched and fighted in Prienai region through different centuries. In 1791the Prienai town was granted municipal rights, a coat of arms and a seal. There are numerous historical monuments in the region; mounds, burial sites, churches and artistic monuments.

Industry in Prienai started at the end of the 18th century after the paper factory was opened. The factory building still stands today. For a long time Prienai used to be famous for its beer, but during the World War II the brewery was destroyed.

The first Catholic Church in Prienai was built around 1609. The present wooden church built in 1850, expanded in 1875, adding to an already beautiful building.

In the 1918 priest F. Martišius founded „Žiburys“ gymnasium, a school specializing in Lithuanian studies of humanities and science. The gymnasium closed during the beginning of W.W.II and reopened in 1995.

The year of independence saw the growth in the Prienai region establishing many factories, producing everything from tomb-stones, cooking oil and felt boots to the best brewed beer in Lithuania at the time. Public and private libraries were opened and banks began to operate.

At the beginning of the first Soviet occupation in Lithuania, Prienai resistance groups were very active. In memory of these people, who died during the fight for Lithuanian independence, monuments stand in Laisves square, on the grounds of „Žiburys“ gymnasium and near the Prienai Pine forest.