The Qakh region of Azerbaijan has a long history dating back to ancient times. Archeological excavations the area had been populated during Eneolithic, Bronze and early Iron Ages. What remains of these early inhabitants' activities indicates they engaged largely in sedentary cultivation, animal-breeding and art. According to historians, the territory of Qakh was a part of the Scythian Kingdom in the 7th century B.C.
With the spread of Christianity throughout the region during the existence of Caucasian Albania, some Christian temples were built in the Qakh district. In the 8th century A.D., Qakh fell under Arab occupation. Starting from the 11th century first Oghuz Turks and later Qipchaq Turks inhabited the area, the region was incorporated into Great Seljuq Empire. Qakh was later a part of Atabeg and Shirvanshah states. With invasion of Hulaguids in Azerbaijan in the 13th century, Mongolian nomadic tribes populated the region. In 1562, by the order of the Safavid Shah Tahmasp I, Ilisu Sultanate was established in Qakh. In the 18th century, Ilisu Sultanate became so powerful that, the Ottoman Emperor conferred its ruler Ali Sultan Bey the highest title of Pasha recognizing him as the Beylerbey of Shaki.
In 1803 the sultanate of Ilisu was annexed to the Russian empire. The ruler of the sultanate, Daniyal, inspired the people to rise against Russian rule in 1844, due to a disagreement between him and the government of Russia. Sultan Daniyel was defeated near the village of İlisu and continued his struggle against Russian along with the leader of the national freedom movement, Sheykh Shamil. Russians burnt Ilisu and divided the territory of the sultanate into mahals (territorial units) and annexed them to the Jar-Balaken daire (territorial unit) converting it into a colony of tsarist Russia. With proclamation of independence of Azerbaijan Democratic Republic in May 1918, Qakh was retained within Azerbaijan. During the Soviet rule, Qakh was established as raion of Azerbaijan SSR in 1930.
The area of the region occupies 1,494 km2 (577 sq mi) and borders Russia on the north, Georgia on the west. It also shares the internal boundaries with Zaqatala Rayon in the northwest, Yevlakh and Samukh regions in the south and Shaki region in the east.