In the latter half of the 17th century, a Lithuanian Evangelical Reformed Church was built (which subsequently collapsed at the beginning of the 18th century) and a parish school was established during the same period.

During the Northern War in the early 18th century, Vyžuonos was subjected to extensive destruction, resulting in its near-total depopulation.

Following the restoration of Lithuania in 1918, a pharmacy, a dairy, a mill, branches of the Lithuanian Riflemen's Union, Pavasarininkai and the Lithuanian Catholic Sobriety Society were established in the area.

[2] During the Nazi German occupation of Lithuania, in July 1941, 67 Jews of the city were executed by an Einsatzgruppen in Vyžuonos forest.

During the Soviet occupation following the World War II, the Šarūnas and Liūtas detachments of Lithuanian partisans were active in the area.