According to Movses Khorenatsi, the name of Sisakan—and subsequently Sisian—was derived from Sisak,[2] a legendary ancestor of the Armenian princely house of Syuni.

[3] Archaeological excavations of tombs and ceramics of the middle Bronze Age found in Sisian have been connected to the Trialeti-Vanadzor culture.

[5] Some scholars identify Tsghuk with Suluqu, a country mentioned in a cuneiform inscription of King Argishti II of Urartu in the 8th century BC.

[6] Between 331 BC and 428 AD, the region of Sisian—known as Sisakan—was part of the ancient Kingdom of Armenia under the reign of the Orontid, Artaxiad and Arsacid dynasties.

[11] In 1247, a Dominican mission, including Simon of Saint-Quentin and Ascelin of Lombardy, sent by Pope Innocent IV, arrived at the great Mongol encampment of the castle of Sisian in Armenia.

[16] At the beginning of the 19th century, many territories of southern Armenia including the region of Sisakan became part of the Russian Empire as a result of the Treaty of Gulistan, signed on 24 October 1813 between Russia and Qajar Iran following the Russo-Persian War of 1804–13.

The Sisian airport no longer operates for civilian aviation and is currently the site of a joint Russian-Armenian military post.

[22][23] Following the independence of Armenia in 1991, Sisian was incorporated into the newly formed Syunik Province based on the 1995 administrative reforms.

Surrounded by the Zangezur Mountains from the west and the Bargushat Mountains from the south, the town is situated on the bank of the Vorotan River, at an average height of 1600 above sea level, only 6 km south of the main highway that connects Armenia with Iran and the region of Nagorno-Karabakh.

The Zorats Karer archaeological site—often referred to in international tourist lore as the Armenian Stonehenge[29]—of the 3rd millennium BC is located 3 km north of Sisian.

The 7th-century Saint Gregory Church of Sisavan (also known as Surp Hovhannes) is among the major historic landmarks of the town, built in 670-689.

Many industrial plants and service firms were opened by the Soviet government, including the production of building materials, reinforced concrete, textile and medical equipment.

Following the independence of Armenia and the resulted economic crisis, most of the industrial and agricultural firms of the Soviet period were forced to close.

With its ancient archaeological sites and attractive nature, tourism is an important sector for Sisian and the region.

The Sisian branch of the Armenian National Agrarian University was opened in 2004, with seven specialties: agronomy, milk and dairy technology, land management and cadastral survey, economics and management of agrarian production, agrifood system accountancy and audit, veterinary sanitary expertise, and animal husbandry.

Football, volleyball, futsal, handball, weightlifting, boxing, wrestling and chess are among the popular sports in Sisian.

The children and youth sport school of the towns was opened in 1961 by the efforts of volleyball player Manvel Amirkhanyan.