The territory, occupied with Ulyanovsk Region now, has been a part of minimum three states: Volga Bulgaria, Kazan Khakanat and Russia.

Archaeology suggests that this territory took place more than 100 thousand years ago. This is evidenced by some Paleolithic sites and founds of Paleolithic tools made of stone and bone, made at the mouth of Cheremshan River, on the Tunguz peninsula.

In the 8th – 9th centuries A.D. this territory was a part of the Early Volga Bulgaria (historic Bulgar state that existed between the 7th and 13th centuries around the confluence of the Volga and Kama rivers). In that time Volga Bulgaria was like a union of nomadic Turkic peoples and Finno-Ugric settled ones.

In the late 14th – early 15th centuries this territory went to seed because of the depredation, made by Timur-i-leng known as Tamerlan in the western tradition, the conqueror came from the Central Asia. In the late 1430-s this land became a part of Kazan Khakanat. As it is known, Kazan Khakanat was conquered by the first Russian tsar Ivan the terrible and became a part of Muscovia in the middle of the 16th century. However, the active Russian expansion on this part of Volga Region begun in the second part of the 17th century only, when the fortification line of Karsunsko-Simbirskaya had been constructed.

The fortification line and fortress of Simbirsk was being constructed for the purpose of defence from the foreign enemies, but firstly it figured in the civil war with Cossacks under Stepan Razin, taken arms against the regime. In the 18th century the colonization went further to the south and fortification line with Simbirsk began losing its strategic importance.

The city of Simbirsk was founded in 1648 by the command of Tsar Alexey Mikhailovich. It was initially a fortified town and Moscow’s border guard post. The period of Simbirsk's settlement was a time of growth and expansion for the Russian feudal state, and of active development of the Volga region. The city was founded under the leadership of Commander Bogdan Matveyevich Khitrovo.

The city first was given the name "Sinbirsk", but later changed to "Simbirsk." There is debate as to the origin and meaning of the name, but the greatest consensus is that it signifies "Seven Winds" referring to the strong and frequent gusts coming off of the Volga. Due to its geographical position it became a centre for trade with Asia. During the 18th century the nobles called the town “Noble’s Nest” as Russia’s rich used to retire here for their holidays. The famous Russian writer Ivan Goncharov was born and lived here.

The history of the region is closely connected with the history of Russia, for example: the region was in thick of the Mongolian and Tatar Yoke, numerous peasant wars, the War of 1812, the Decembrist Revolt, revolutions and world wars. Simbirsk was the birthplace of many famous writers, poets, and statesmen: I.A.Goncharov, D.V.Davydov, N.M.Yazykov, D.D.Minaev, N.M.Karamzin, A.F.Kerenski among them.

The establishment of the Simbirsk Province in 1796 came as an important milestone, and over the next century grew to be one of the largest in the Volga region. The formation of the Simbirsk province dates back to the 19th century. In 1924 Simbirsk was renamed to Ulyanovsk (as Simbirsk was a birthplace of Ulyanov-Lenin). 1943 is the year of formation of the Ulyanovsk region with the centre in Ulyanovsk.

During the Second World War Ulyanovsk Region was one of the places where different facilities, institutions and organizations had been evoked from the western districts of the country.

Different industrial facilities and institutions appeared in the region in the 1950-1960-s, among them – Scientific Research Institute of Atomic Reactors. On the same occasion the airport of Ulyanovsk and highway bridge over Volga. The river of Volga (the largest one on the territory of Russia) divides the region in two parts, the elevated Right Bank and low-lying Left Bank, or Zavolzhye.