Eišiškės is mentioned for the first time in the Treaty of Königsberg (1384) between Grand Duke Vytautas and the Teutonic Knights.
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 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 the abolition of serfdom.
After a 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 the Polish Armia Krajowa, Nazi Wehrmacht, and Soviet Red Army.
Eišiškės is mentioned for the first time in the Treaty of Königsberg (1384) between Grand Duke Vytautas and the Teutonic Knights. 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 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 the abolition of serfdom. After a 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 the Polish Armia Krajowa, Nazi Wehrmacht, and Soviet Red Army.
Eišiškės