Ukmerge was first mentioned in 1225, and named as a settlement in 1333. It was essentially a wooden fortress that stood on a hill, near the confluence of the Vilkmerge River and the Šventoji River. Ukmerge was attacked by the Teutonic Knights and the Livonian Order in 1333, 1365, 1378, 1386, and even in 1391, already after the Christianization of Lithuania in 1387. During the last attack, Ukmerge was burned to the ground and had to be completely rebuilt.

The region began to adopt Christianity, along with the rest of Lithuania, in 1386. In the following year, 1387, its first Catholic church, St. Peter and St. Paul, was built. It was one of the first Roman Catholic churches established in Lithuania. The town was granted municipal rights at some time after the Battle of Wilkomierz in 1435, and written sources dating from 1486 referred to it as a city. King Sigismund the Old confirmed these rights. During the times of the Polish–Lithuanian Commonwealth, the city had been the center of powiat in the Vilnius Voivodeship.

In 1655, the Swedish and Russian armies plundered the city. Because of these incessant wars, the growth of Ukmerge suffered many setbacks. Jews began to settle in the city in the late 17th century, and built a synagogue and a cemetery. In the years 1711-1712, the bubonic plague swept through the town and wreaked havoc upon its population. In 1792, by the initiative of the city's representative in the Great Sejm, Józef Dominik Kossakowski, King Stanislaw August Poniatowski renewed the town's municipal rights and gave it its current coat of arms.