The area is often called the "cradle of civilization". The ancient writing called cuneiform was first used around 3000 BC by the Sumerians. Historically important cities in Mesopotamia included Uruk, Nippur, Nineveh, and Babylon.

Major territorial states were the Akkadian kingdom, the Third Dynasty of Ur, and the Assyrian Empire. Some of the important historical Mesopotamian leaders were Ur-Nammu (king of Ur), Sargon of Akkad (the founder of the Akkadian kingdom), Hammurabi (who established the Old Babylonian state), and Tiglath-Pileser I (who started the Assyrian Empire).

Many advances in technology were made by the ancient Sumerians and Mesopotamians, such as irrigation, trade by river, and floodcontrol. Mesopotamians had agriculture and domesticated animals, or livestock, from the earliest records. Babylon is probably the first city built by settled people. Mesopotamia also was the place where the wheel was first used. First it was a potter's wheel that was used to make clay pots, then Sumerians adapted it for transport.