By the early third millennium B.C.E., a dozen or so cities had arisen throughout Babylonia. These early urban areas thrived under the rule of the Akkadians (ca. 2350–1900 B.C.E.), and especially during the reign of the Akkadian king Sargon the Great (ca. 2334–ca. 2279 B.C.E.). Following the Akkadians, Babylonia fell under the control of a succession of invaders, including the Elamites from what is now Iran and the Amorites who lived west of the Euphrates. By about 1900 B.C.E., the empire these peoples created eventually expanded to reach the Mediterranean Sea in the west, the Persian Gulf in the east, Anatolia to the north, and the Arabian Desert to the south.

Throughout its history, Babylonian society took as its model the culture that arose in the southern region of Sumer during the fourth millennium B.C.E. Sumerian influence remained strong even though power in the region changed hands several times, and many Sumerian cultural elements persisted for thousands of years. These included cuneiform writing, polytheistic religions, and strict social structures and king-centered political organization.

The post-Akkadian history of Babylonia is divided into three eras: the Old Babylonian Period (ca. 2000–1595 B.C.E.), the Middle Babylonian Period (ca. 1595–1000 B.C.E.) and the Neo-Babylonian Period (612–539 B.C.E.). The Old Babylonian Period was marked by Amorite control over the region (the Amorites were a Semitic people living west of the Euphrates River). It is during this period that the renowned King Hammurabi (r. 1792–1750 B.C.E.) ruled and developed a set of laws, which is the oldest, complete law code still in existence today.

After Hammurabi, a series of weak kings came to the throne. By 1595 B.C.E., Babylonia had been conquered by the Hittites from Anatolia and the Kassites from what is now Iran. Nevertheless, the religious, political, and social institutions that defined Babylonia continued during these successor states until the Persians conquered the region in the sixth century B.C.E.

Babylonian gods were associated with aspects of nature, such as the wind, rain, and water. The most important ones were seen as the founders and sometimes patrons of the major cities in the region. The Babylonians viewed their gods as fickle, and as likely to harm them as protect them. An official class of priests acted as intermediaries between the citizens and their patron deity, offering sacrifices to honor or appease the gods in hopes of protecting the city and ensuring its prosperity.

An innovative people, the Babylonians built on the earlier developments in the area of mathematics. They developed a base-60 numerical system whose influence is preserved to this day in the division of hours into 60 minutes and minutes into 60 seconds. The division of the circle into 360 degrees is also a legacy of the Babylonians. Their mathematical abilities also enabled them to develop the engineering skills needed to build impressive projects such as extensive irrigation systems, strong defensive walls for their cities, and the massive ziggurats. Babylonians were also among the world's earliest astronomers, building observatories near their temple sites. Babylonian astronomy was inspired by the belief that the gods communicated to humans through heavenly signs, which led them to identify constellations, create the concept of the zodiac, and develop astronomical tables to predict eclipses and other heavenly phenomena. Their fascination with the skies reflected the widespread notion that what occurred in heaven provided clues to future events on earth.