The great cities of Mesopotamia ("the land between two rivers") developed prior to the late 4th millennium BCE along two rivers – the Tigris and Euphrates – and were fully established by the Early Dynastic period (circa 2900 to circa 2350/2334 BCE). Many of these cities became famous in their own time, and among these are the twelve below. The dates of their approximate founding follow the names:

There were many other great cities in Mesopotamia and surrounding regions, of course, including Aratta – whose precise location has not been identified, but the archaeological site of Konar Sandal, near Jiroft (Kerman Province, Iran) seems increasingly likely – Susa, Persepolis, Kalhu/Nimrud, and Dur-Sharrukin, as well as many others, which all played important roles in the history of the region.

The twelve above, however, were not only famous in their own time but, in many cases, became legendary through the works of later Greek writers and, in the modern age, have yielded some of the most significant archaeological finds in the region.

Cities in Mesopotamia usually began as small villages that grew into trading hubs or were known as important religious sites. A city lacking in valuable trade goods could still become prosperous as a site for religious pilgrimages, with the offerings visitors left at the temple complex and hospitality venues catering to visitors. Religion was central to every Mesopotamian city, as explained by scholar Gwendolyn Leick:

Myths describe cities such as Babylon to have been created by the gods to be their dwelling place. Each city was thus intimately connected to a particular deity, whose image resided in the temple. Ur, for instance, was the seat of the moon god Nanna-Suen, Sippar of the sun god Utu-Shamash, and so forth. The fate of individual cities was linked with the prestige and popularity of their main deity.

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Rivalry between these city-states was often heated, and each tried to outdo the others with the largest ziggurat, the most majestic walls, cultivated public gardens and parks, and, of course, the most robust economy that made such works possible. When a city triumphed in creating some amazing wonder, a festival was held, and when a city fell, it was mourned, notably through the genre known as Mesopotamian city laments.

The following are brief descriptions of twelve of the greatest of these cities, what they were famous for, and how they passed into memory.

Nineveh (modern-day Mosul, Iraq) is best known from the biblical book of Jonah and other references in the Bible, but it had a long history before those narratives were written. The city grew from a small settlement circa 6000 BCE to a great religious center honoring Inanna/Ishtar by 3000 BCE.

It reached its peak during the Neo-Assyrian Empire when Sennacherib (reign 705 to 681 BCE) made it his capital and beautified it with public parks, gardens, and an immense palace complex. Recent scholarship suggests the famous Hanging Gardens of Babylon were actually at Nineveh, commissioned by Sennacherib, and later Greek writers confused the two cities.

Nineveh continued to flourish after Sennacherib and became the site of the famous library of Ashurbanipal (reign 668 to 627 BCE), which held over 30,000 texts. The city was destroyed in 612 BCE by a coalition of Medes, Babylonians, and Persians as the Neo-Assyrian Empire fell.

Kish (modern Tell al-Uhaymir, Iraq) was a settlement during the Ubaid period (circa 6500 to 4000 BCE), but had become a city by circa 5000 BCE and lasted through the 8th century CE, making it one of the oldest and continuously inhabited cities in Mesopotamia. Early on, it was an important religious site dedicated to Inanna/Ishtar and her consort-father Enki/Ea, contributing to its prosperity.

According to the Sumerian King List, Kish was the first city upon which "kingship descended" after the Great Flood. The city became so prosperous and powerful that the title "King of Kish" came to be understood to mean the ruler of all of Sumer. Sargon of Akkad (reign 2334 to 2279 BCE) famously took this title after establishing the Akkadian Empire, which did, in fact, rule over all of Sumer.

Kish is notable as a seat of learning, boasting many scribal schools, monumental architecture, and winning the first war in recorded history, when King Enmebaragesi of Kish defeated Elam in 2700 BCE. The city is also notable as the only one with a female monarch, Kubaba, who had formerly been an innkeeper. Kish declined during the Neo-Assyrian and Persian periods and was finally abandoned at some point after 750.

Eridu (modern Abu Shahrein, Iraq) was considered the first city in the world by the Sumerians and, according to the Sumerian King List, "After the kingship descended from heaven, the kingship was in Eridu", establishing the city as the site where the gods created order on earth in the form of a monarchy that would make laws and maintain a stable society.

The city was never a dynastic seat but among the most important religious sites, dedicated to the god of wisdom and magic, Enki/Ea, and is featured in some of the most significant works of Mesopotamian literature, including the Eridu Genesis, the Atrahasis, the Myth of Adapa, and Inanna and the God of Wisdom.

Eridu remained an important religious site and trade center until it was abandoned sometime around the year 600 BCE. The most likely cause of its fall is thought to be overuse of the land.

Uruk (modern Warka, Iraq) became the most powerful and prosperous city in ancient Mesopotamia and is thought to have given Iraq its name. Its name has also come to define the Uruk period (circa 4000 to 3100 BCE) in Mesopotamian history when urbanization expanded, and many of the most significant aspects of civilization were invented or developed, among them, writing, mass-produced goods, monumental architecture in the form of the ziggurat, and the concept of personal identification in the form of the cylinder seal. It is also famous for its king, Gilgamesh, best known as the central character in the Epic of Gilgamesh, the oldest piece of literature in the world.

Uruk is regarded as the first true city in history, and the site where trade in ancient Mesopotamia first flourished and spread outwards. Artifacts from Uruk have been found in almost every site excavated in the region as well as in Egypt. The city's patron deity, Inanna/Ishtar, was among the most popular in Mesopotamia, and so Uruk prospered from religious pilgrimages as well as trade. The city became so powerful that it inspired the foundation and construction of others, thereby encouraging widespread urbanization.

The city was continuously inhabited from its establishment through the 7th century, when it was abandoned during the Arab Muslim conquest of the region.

Nippur (modern Nuffar, Iraq) began, as with many of the others, as a small settlement in the Ubaid period and grew into an important cultural and religious center before the Early Dynastic period in Mesopotamia. The patron deity was Enlil, "Lord of the Winds," though Inanna/Ishtar and Gula, goddess of healing, were also worshiped there. Nippur was always regarded as a sacred city and pilgrimage site, and so it is hardly surprising that it supported many scribal schools, which, among other works, recorded the sacred stories of the gods now known as Mesopotamian mythology.

Inscriptions found in the ruins of Nippur suggest it was honored as a sacred site by many kings beginning circa 2700 BCE with Enmebaragesi of Kish and including Gilgamesh of Uruk, Sargon of Akkad, and Ur-Nammu of Ur. The city lost prestige when its sacred associations were removed by Hammurabi (reign 1792 to 1750 BCE) and transferred to Babylon, and the city seems to have been damaged in the Elamite invasion of 1750 BCE.

The Temple of Enlil at Nippur (the Ekur) was restored by the Kassites, as was the surrounding city, circa 1375 BCE, and Nippur continued as an important cultural center until the 9th century, although few may have actually lived there. It was abandoned sometime in the 13th century, and whatever was left of the city fell into ruin.

Ur (modern Tell el-Muqayyar, Iraq) was originally a small village that grew into a large port city on the Persian Gulf. Ur is mentioned in the biblical book of Genesis and became famous in the early 20th century, when Sir Leonard Wooley excavated the site and found the tomb he called the "Great Death Pit," containing treasures including the headdress of Queen Puabi and the Royal Standard of Ur.

Ur was favored by the kings of the Akkadian Empire, and Sargon the Great placed his daughter, Enheduanna (circa 2300), as high priestess there. The city reached its height during the Ur III period (circa 2112 to circa 2004 BCE) under the reign of Ur-Nammu (circa 2112 to 2094 BCE) and his son Shulgi of Ur (2094 to circa 2046 BCE). This period, also known as the Sumerian Renaissance, saw a proliferation of scribal schools, architectural developments, and improvements to the infrastructure.

Shulgi built a great wall to protect Ur from invasion, but it was so long that it could not be properly manned and was not anchored at either end. In 1750 BCE, the Amorites simply walked around the wall to attack Ur, and the Elamites breached it, ending not only Ur but also the Sumerian civilization.

Sippar (modern Tell Abu Habbah, Iraq, near Baghdad) was first settled in the late Ubaid period but flourished from the Uruk period through the 1st millennium BCE The site became famous in the late 19th century, when the Babylonian Map of the World – a clay tablet of the map of the world with Babylon as its center (circa 9th century BCE) – was discovered there circa 1882.

The patron deity of the city was Utu-Shamash by the Akkadian period (2350/2334 to 2154 BCE), and the Sumerian King List shows Sippar as the fourth city to receive kingship from the gods, attesting to its high standing. The city became famous in its time for the production of cylinder seals and wool, and the famous Code of Hammurabi is thought to have first been erected at Sippar.

The city declined during the period of the Achaemenid Empire (circa 550 to 330 BCE) but was still extant during the time of the Parthian Empire (247 BCE to 224 CE), after which it seems to have been abandoned.

Mari (modern Tell Hariri, Syria) was a marvel of engineering and design and became the most prosperous city of Northern Mesopotamia. Unlike many of the other cities, Mari did not evolve from an earlier settlement but was preplanned as a new city. The site was inland from the Euphrates River, and so a 'linking canal' was built, drawing water from the river to the city, and then smaller canals drew from this to irrigate crops.

The city was carefully designed to rise gradually upwards with a drainage system beneath the streets and around the lower part to carry away rainwater and waste. The site was chosen for its position on a popular trade route, and so the city prospered not only through trade but also by collecting tolls from every merchant who passed through. The deities of the city were both Sumerian and Semitic, with temples honoring Dagan and Inanna/Ishtar among others.

Mari reached its height during the reign of Zimri-Lim (1775 to 1761 BCE), who had allied himself with Hammurabi of Babylon, who then turned on him and destroyed the city circa 1761. The ruined canal system overflowed, softening the mud-brick foundations of the buildings and causing them to collapse.

Although the site continued to be inhabited up through the 3rd century BCE, it was a ruin by circa 1757 BCE. Today, the site is best known for the Mari Tablets, between 15,000 and 25,000 clay tablets baked in the fires of the city's fall and so perfectly preserved, as also happened at Nineveh with the library of Ashurbanipal.

Lagash (modern Al-Shatrah, Iraq) grew from a small settlement in the Uruk period to a city by the Early Dynastic I period. It prospered through trade owing to its favorable position between the Tigris and Euphrates rivers and by canals leading water into the city and then to smaller irrigation ditches that encouraged abundant harvests.

Many of the tablets found in the ruins of the city attest to grand building projects, including temples, palaces, and canals. The city first fell to King Lugalzagesi of Uruk in circa 2350 BCE, was rebuilt by Sargon of Akkad, and reached its height under the reign of Gudea (circa 2144 to 2124 BCE). Gudea devoted himself to building shrines and temples and is mentioned in the text of The Building of Ningirsu's Temple, in which the goddess Nanshe interprets his dream of constructing a temple to Ningirsu, the city's patron deity (similar to Ninurta), along with the mother goddess Bau/Babu.

Lagash aligned itself with Ur during the Ur III period, and, when that city fell circa 1750 BCE, Lagash began to decline. It was abandoned by circa 1600 BCE.

Ashur (also given as Assur, modern Qal'at Sherqat, al-Shirqat District, Iraq) was first established during the Early Dynastic I Period, served as an outpost and trade center of the Akkadian Empire, and continued to flourish through trade during the Ur III period. It was commercially linked to the famous trade center of Karum Kanesh in Anatolia (Asia Minor) and also profited from religious pilgrimage and offerings to the patron god Ashur and the goddess Ishtar.

Circa 1900, the most famous incarnation of the city was established under the Assyrians, who made it their capital. All the great Assyrian kings launched their military campaigns from Ashur and brought back booty from their conquests to fill the city's treasury. Assyrian kings were also buried in the city, except for Sargon II, whose body was lost in battle.

Even after King Ashurnasirpal II (884 to 859) moved the capital to Kalhu, Ashur still remained an important trade, cultural, and religious center until it was sacked in 612 BCE by the coalition of Babylonians, Medes, and Persians, who also took the other great Neo-Assyrian cities. Ashur was taken by the Roman Empire circa 116 and destroyed by the Sassanian Persians under their king Ardashir I (reign 224 to 240), but it remained populated up through the 14th century when it was abandoned.

Akkad (also given as Agade, location unknown) is thought to have been built by Sargon of Akkad circa 2350/2334 BCE, although he may have only restored an earlier city on the same site. Prior to Sargon's rise, Lugalzagesi of Uruk had conquered Sumer, and Sargon, learning from these campaigns, defeated Lugalzagesi and founded the first multinational empire in the world, encompassing modern-day Iraq, Jordan, Kuwait, part of Lebanon, Syria, part of Asia Minor, and possibly as far as Crete.

The city became fabulously wealthy and reached its height under the reign of Sargon's grandson, Naram-Sin (2254 to 2218), the greatest of the Akkadian kings. The patron deity of the city was Ishtar, who was credited with the kings' victories and the city's prosperity. The Akkadian Empire provided the stability that enabled developments in the arts and sciences, but at the same time, it was beset by rebellions throughout its history by city-states and regions that objected to its heavy-handed policies.

According to later Sumerian scribes, Akkad fell to the invading Gutians circa 2154 BCE. Modern scholarship, however, suggests that climate change weakened the city and its empire, allowing for the victory by the Gutians, which would have been impossible earlier in its history.

Babylon (modern Hillah, Iraq) is easily the most famous Mesopotamian city owing to its mention in the Bible. It was originally a small town established at some point during the Akkadian period and was a religious and cultural center by the time of the Akkadian king Shar-Kali-Sharri (2217 to 2193 BCE). The city reached its height during the reign of Hammurabi, who made Babylon the capital of his empire and the largest city in the world at that time, with a population estimated at over 200,000 people.

After Hammurabi, the city declined but revived during the Middle Assyrian period (circa 1365 to 1053), and by the time of the Neo-Assyrian Empire, it was strong enough to mount resistance to Assyrian rulers. It was completely destroyed by the Neo-Assyrian king Sennacherib in 689 BCE (which led to his assassination) and rebuilt by his son Esarhaddon.

After the fall of the Neo-Assyrian Empire in 612 BCE, Babylon again flourished during the reign of Nebuchadnezzar II (604 to 561 BCE), who revitalized the city and built the famous Ishtar Gate. He is also credited with the completion of the great ziggurat (the Etemenanki, "House of the Foundation of Heaven and Earth"), which is thought to have inspired the biblical Tower of Babel and also with the construction of the Hanging Gardens of Babylon (which, as noted, may actually have been at Nineveh).

The city continued to flourish under the Achaemenid Empire after it was taken by Cyrus the Great in 539 BCE, but it declined after the death of Alexander the Great, who had conquered the region. Babylon never again reached its earlier heights and slowly declined further until it was abandoned by the 7th century.