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Akkadian is divided into several varieties based on geography and historical period:

One of the earliest known Akkadian inscriptions was found on a bowl at Ur, addressed to the very early pre-Sargonic king Meskiagnunna of Ur (c. 2485 –2450 BC) by his queen Gan-saman, who is thought to have been from Akkad. The Akkadian Empire, established by Sargon of Akkad, introduced the Akkadian language (the "language of Akkad ") as a written language, adapting Sumerian cuneiform orthography for the purpose. During the Middle Bronze Age (Old Assyrian and Old Babylonian period), the language virtually displaced Sumerian, which is assumed to have been extinct as a living language by the 18th century BC.

Old Akkadian, which was used until the end of the 3rd millennium BC, differed from both Babylonian and Assyrian, and was displaced by these dialects. By the 21st century BC Babylonian and Assyrian, which were to become the primary dialects, were easily distinguishable. Old Babylonian, along with the closely related dialect Mariotic, is clearly more innovative than the Old Assyrian dialect and the more distantly related Eblaite language. For this reason, forms like lu-prus ('I will decide') were first encountered in Old Babylonian instead of the older la-prus.

While generally more archaic, Assyrian developed certain innovations as well, such as the "Assyrian vowel harmony ". Eblaite was even more so, retaining a productive dual and a relative pronoun declined in case, number and gender. Both of these had already disappeared in Old Akkadian. Over 20,000 cuneiform tablets in Old Assyrian have been recovered from the Kültepe site in Anatolia.Most of the archaeological evidence is typical of Anatolia rather than of Assyria, but the use both of cuneiform and the dialect is the best indication of Assyrian presence.

Old Babylonian was the language of king Hammurabi and his code, which is one of the oldest collections of laws in the world. (see Code of Ur-Nammu.) Old Assyrian developed as well during the second millennium BC, but because it was a purely popular language — kings wrote in Babylonian — few long texts are preserved. It was, however, notably used in the correspondence of Assyrian traders in Anatolia in the 20th-18th centuries BC and that even led to its temporary adoption as a diplomatic language by various local Anatolian polities during that time.

The Middle Babylonian period started in the 16th century BC. The division is marked by the Kassite invasion of Babylonia around 1550 BC. The Kassites, who reigned for 300 years, gave up their own language in favor of Akkadian, but they had little influence on the language. At its apogee, Middle Babylonian was the written language of diplomacy of the entire Ancient Near East, including Egypt (Amarna Period). During this period, a large number of loan words were included in the language from Northwest Semitic languages and Hurrian. However, the use of these words was confined to the fringes of the Akkadian-speaking territory.

From 1500 BC onwards, the Assyrian language is termed Middle Assyrian. It was the language of the Middle Assyrian Empire. However, the Babylonian cultural influence was strong and the Assyrians wrote royal inscriptions, religious and most scholarly texts in Middle Babylonian, whereas Middle Assyrian was used mostly in letters and administrative documents.

During the first millennium BC, Akkadian progressively lost its status as a lingua franca. In the beginning, from around 1000 BC, Akkadian and Aramaic were of equal status, as can be seen in the number of copied texts: clay tablets were written in Akkadian, while scribes writing on papyrus and leather used Aramaic. From this period on, one speaks of Neo-Babylonian and Neo-Assyrian.

Neo-Assyrian received an upswing in popularity in the 10th century BC when the Assyrian kingdom became a major power with the Neo-Assyrian Empire. During the existence of that empire, however, Neo-Assyrian began to turn into a chancellery language, being marginalized by Old Aramaic. The dominance of the Neo-Assyrian Empire under Tiglath-Pileser III over Aram-Damascus in the middle of the 8th century led to the establishment of Aramaic as a lingua franca of the empire, rather than it being eclipsed by Akkadian. Texts written 'exclusively' in Neo-Assyrian disappear within 10 years of Nineveh 's destruction in 612 BC. Under the Achaemenids, Aramaic continued to prosper, but Assyrian continued its decline. The language's final demise came about during the Hellenistic period when it was further marginalized by Koine Greek, even though Neo-Assyrian cuneiform remained in use in literary tradition well into Parthian times.

Similarly, the Persian conquest of the Mesopotamian kingdoms contributed to the decline of Babylonian, from that point on known as Late Babylonian, as a popular language. However, the language was still used in its written form. Even after the Greek invasion under Alexander the Great in the 4th century BC, Akkadian was still a contender as a written language, but spoken Akkadian was likely extinct by this time, or at least rarely used. The last positively identified Akkadian text comes from the 1st century AD. The latest known text in cuneiform Babylonian is an astronomical almanac dated to 79/80 AD. However, the latest cuneiform texts are almost entirely written in Sumerian logograms.