According to Armenian tradition, Nakhichevan was founded by Noah, of the Abrahamic religions. The oldest material culture artifacts found in the region date back to the Neolithic Age. The region was part of the states of Mannae, Urartu and Media. It became part of the Satrapy of Armenia under Achaemenid Persia circa 521 BC. After Alexander the Great's death (323 BC) various Macedonian generals such as Neoptolemus tried to take control of the region but ultimately failed and a native dynasty of Orontids flourished until Armenia was conquered by Antiochus III the Great. In 189 BC, Nakhichevan part of the new Kingdom of Armenia established by Artaxias I. Within the kingdom, the region of present-day Nakhichevan was part of the Ayrarat, Vaspurakan and Syunik provinces. In 428, the Armenian Arshakuni monarchy was abolished and Nakhichevan was annexed by Sassanid Persians, and in 623 by the Byzantine Empire. From 640 on, Arabs invaded Nakhichevan and undertook many campaigns in the area crushing all resistance. It was finally conquered by the Arabs thirteen years later and became part of the autonomous Principality of Armenia under Arab rule. In 8th century, Nakhichevan was one of the scenes of Babak Khorramdin's uprising against the Arabs. Nakhichevan was finally liberated from Arab rule in the 10th century by Bagratid King Smbat I and handed over to the princes of Syunik. In the 11th century, however, it was conquered by the Seljuq Turks.
12th century, the city of Nakhichevan became the capital of the state of Atabegs of Azerbaijan, also known as Ildegizid state, which included most of Iranian Azerbaijan and significant part of South Caucasus. The magnificent 12th century mausoleum of Momine khatun, the wife of Ildegizid ruler, Great Atabeg Jahan Pehlevan, is the main attraction of modern Nakhichevan. At its heydays, the Ildegizid authority in Nakhichevan and some other areas of South Caucasus was contested by the Kingdom of Georgia. The Armeno-Georgian princely house of Zacharids frequently raided the region when the Atabeg state was in decline in the early years of the 13th century. It was then plundered by invading Mongols in 1220 and Khwarezmians in 1225 and became part of Mongol Empire in 1236 when the Caucasus was invaded by Chormaqan.
In the 15th century, the territory of Nakhichevan became part of the states of Kara Koyunlu and Ak Koyunlu. In the 16th century control of the region passed to the Turkic-speaking Safavid dynasty of Persia. Because of its geographic position, it frequently suffered during the wars between Persia and the Ottoman Empire in 14th – 18th centuries. In 1604, Shah Abbas I Safavi, concerned that the lands of Nakhichevan and the surrounding areas would pass into Ottoman hands, decided to institute a scorched earth policy. He forced most of the local population, regardless of ethnicity or religion, to leave their homes and move deeper into Persia. Many settled in a neighborhood of Isfahan that was named New Julfa since most of the residents were from the original Julfa (a predominantly Armenian town which was looted and burned). The Nakhichevan khanate emerged in the region in 1747 after the death of Nadir Shah Afshar, the ruler of Persia.