First mentioned in 1408 as Тягянякяча (Tyagyanyakyacha) in a document in Old Slavonic (the term is of Cuman origin), the town was known in the Middle Ages as Tighina in Moldavian sources and later as Bender in Ottoman sources. The fortress and the city were called Bender for the most part of the time they were a rayah of the Ottomans (1538-1812), and during most of the time they belonged to the Russian Empire (1828-1917). They were known as Tighina (Тигина) in the Principality of Moldavia, in the early part of the Russian Empire period (1812-1828), and during the time the city belonged to Romania (1918-1940; 1941-1944).

The city is part of the historical region of Bessarabia. During the Soviet period the city was known in the Moldavian SSR as Бендер (Bender) in Moldovan (Romanian) written then with the Cyrillic alphabet, and as Бендéры (Bendery) in Russian. In the independent Moldova, officially it is known as Bender, but otherwise both names Bender and Tighina are used.

The town was first mentioned as an important customs post in a commerce grant issued by the Moldavian voivode Alexander the Good to the merchants of Lviv on October 8, 1408. The name "Tighina" is found in documents from the second half of the 15th century. The town was the main Moldavian customs point on the commercial road linking the country to Tatar Crimea. During his reign of Moldavia, Stephen III had a small wooden fort built in the town to defend the settlement from Tatar raids.

In 1538, the Ottoman sultan Suleiman the Magnificent conquered the town from Moldavia, and renamed it Bender. Its fortifications were developed into a full fortress under the same name under the supervision of the Turkish architect Koji Mimar Sinan. The Ottomans used it to keep the pressure on Moldavia.

In the 18th century, the fort's area was expanded and modernized by the prince of Moldavia Antioh Cantemir, who carried out these works under Ottoman supervision.

In 1713, the fortress, the town, and the neighboring village Varniţa were the site of skirmishes (kalabalik) between Charles XII of Sweden, who had taken refuge there with the Cossack Hetman Ivan Mazepa after their defeat in the Battle of Poltava, and Turks who wished to enforce the departure of the Swedish king.

During the second half of the 18th century, the fortress fell three times to the Russians during the Russo-Turkish Wars (in 1770, 1789, and finally in 1806 without a fight).

Along with Bessarabia, the city was annexed to the Russian Empire in 1812, and remained part of the Russian Governorate of Bessarabia until 1917.

Tighina was part of the Moldavian Democratic Republic in 1917-1918, and after 1918, as part of Bessarabia, the city belonged to Romania, where it was the seat of Tighina County.

Along with Bessarabia, the city was occupied by the Soviet Union on June 28, 1940, following an ultimatum. In the course of World War II, it was retaken by Romania in July 1941, and again by the USSR in August 1944.