Eišiškės is mentioned for the first time in the Treaty of Königsberg (1384) between Vytautas the Great and the Teutonic Knights. According to the Lithuanian Chronicles, the town was named after Eikšys, possibly one of the sons of Karijotas. East of the town there is a castle site, dating back from the 14th–15th centuries. Historian Ignas Jonynas argued that Anna, Grand Duchess of Lithuania and wife of Vytautas the Great was a sister of Sudimantas, a nobleman from Eišiškės and commander of Vytautas' army.An important route, connecting Vilnius, Hrodna, and Warsaw, ran through the town. Protected by the castle and boasting a church built by Vytautas, the town became one of the important trading centers in the Grand Duchy of Lithuania. It had a court and here nobles gathered for a sejmik.

Eišiškės was sacked and burned in 1655 during the Muscovite invasion and in 1706 during the Great Northern War. The town lost majority of inhabitants and lost its former status as a trade center. At the end of the 17th century, in hopes to revive the economy Eišiškės were granted Magdeburg rights and became known for its horse and cattle markets. The former market square and surrounding streets are protected as urban heritage since 1969^. The town's importance decreased after the partitions of the Polish–Lithuanian Commonwealth, especially after it was sacked during the French invasion of Russia. However, the town grew rapidly following the Uprising of 1863 and abolition of serfdom. After few devastating fires, residents started constructing brick buildings. The town continued to be known for its markets and for its carriages. Eišiškės was part of the Nowogródek Voivodeship of the Second Polish Republic during the interwar years. During World War II, the town witnessed some fighting between Polish Armia Krajowa, Nazi Wehrmacht, and Soviet Red Army.

Jewish history

Romantic Jewish legends claim that in the former Jewish cemeteries there were tombstones dating from 1171 or 1097, making Eišiškės one of the oldest Jewish settlements in Eastern Europe. However reliable data about Jewish residents comes only from the 18th century. By that time they already had a synagogue and two Jewish cemeteries, and accounted for about half of the population. As the town grew, the proportion of Jewish residents increased, hitting a peak of 80% in 1820. By 1850, the Jewish community had two beth midrashes. They dominated trade and crafts: in 1935 out of 117 enterprises, 106 belonged to Jews.

On September 25–26, 1941, an Einsatzgruppen unit entered Eišiškės and killed 3,446 Jews from Eišiškės and about 1,500 Jews from neighboring towns and villages. Men's bodies were buried in a trench, dug around the old Jewish cemetery to protect it from accidental cultivation by local farmers. The old cemetery is now a site of remembrance with a memorial stone in three languages. The new cemetery was destroyed in 1953 and turned into a yard of a kindergarten. Most of the private Jewish buildings survive and are protected as part of the urban heritage. One beth midrash is now a library, another was demolished. The synagogue was reconstructed into a sport hall and is now abandoned. The history of Eišiškės (Eishyshok) shtetl has been documented in the book There Once Was A World by Yaffa Eliach, professor at Brooklyn College.