In ancient times, the region of Karabagh and most of eastern Transcaucasia was inhabited by a people called Albanians, not to be confused with the people of the same name now living in the Balkans. According to the Greek geographer Strabo (1st c. B.C.), Karabagh, which then encompassed both the mountainous Nagorno-Karabagh of today and the larger lowlands, surrounding it, had a highly developed economy and was famous for its cavalry. Caucasian Albanians maintained close contacts with the Armenians. In the fifth century, shortly after the Armenians converted to Christianity, the Albanians too adopted the Armenian brand of Christianity. The first church established in Karabagh, in the region now known as Martuni, was established by Gregory the Illuminator, first Catholicos of Armenia. Tradition has it that Mesrob Mashtotz, the monk who created the Armenian alphabet, founded the first school in Karabagh.

Given the centrality of religion to social life during that period, it is not surprising that in the following two centuries the Albanians merged with the Armenians. The nobility intermarried, the region's bishops were often Armenians, and by the seventh century the separate identity of the Albanians was lost.

The territories of both Mountainous Karabagh and the larger surrounding lowlands became parts of the Armenian provinces of Utik, Sunik and Artsakh. In the seventh and eighth centuries much of this area was conquered by Arabs, who converted a portion of the population to Islam. In Karabagh, only a very small minority was converted. The situation of Karabagh changed radically in the eleventh century when the ethnic Turkish invasions began. The Turks had emerged from Central Asia, had conquered Iran, and founded the Seljuk Turkish dynasty, which first raided,

then invaded Armenia. From 1020 on, these invasions destroyed much of Armenia, and Karabagh, especially its lowlands, suffered greatly. By the mid-eleventh century, the Armenian kingdom was destroyed. But the feudal principality of Sunik, which occupied the mountainous territory in the southeast of today's Soviet Armenia and Mountainous Karabagh survived and became beacons to the rest of Armenia. In the following centuries, thousands of Armenians found refuge in Karabagh, under the protection of native lords.

During the seventeenth and eighteenth centuries Karabagh gave rise to the pioneers of the Armenian emancipatory struggle. Representatives of the region attempted to interest the monarchs of Russia and other European powers in embarking on a "crusade" to liberate the Armenian plateau, the eastern portions of which were occupied by the Ottoman Turkish and Persian Empires. During the 1720's, the rebellion of the Armenians of Sunik and Karabagh, led by David Beg, achieved notable though temporary success. The Russian Empire, expanding southwards in the Transcaucasus, annexed the territory of Karabagh in 1805.

The Russian annexation of Karabagh was officially recognized by Persia in the Treaty of Gulistan in 1813. Thus Karabagh came into the Russian Empire earlier than the areas of Yerevan and Nakhichevan, which were ceded to Russia by Persia in the Treaty of Turkmenchai in 1828. This earlier annexation benefited Karabagh in some ways, but also created a major problem for the future. Because of the time it came into the Russian empire, Karabagh was made part of Elizavetpol Province, which later became Azerbaijan. Administratively, then, Karabagh could not be joined in 1813 to the as-yet un-annexed Armenian territories of which its history and population made it a natural part. Yerevan and Nakhichevan, when they were attached to the Tzarist empire in 1828, were organized in the Armianskoy region, later the Yerevan province. Here, as in other empires, decisions made by colonial administrators laid the foundations for future difficulties.