The "mound builders" of early North America lived throughout what are now the Ohio Valley and the Mississippi regions. The earliest group was probably the Adena people, who flourished from 1000 BCE to 200 BCE. They built mounds throughout North America, from Wisconsin to Mississippi.

The Great Serpent Mound in southern Ohio is one of the few surviving relics of the mound builders. It is a 1,330-foot-long, three-foot-high prehistoric effigy mound. The earliest records say it was a depiction of a serpent that was swallowing an egg. One of the more interesting theories as to the origin of the shape is that it represents an explanation of the phases of the moon, by the representation of a snake swallowing it.

It is unclear who built the Great Serpent Mound. The Adena culture built structures like it, and they built burial grounds that are located near the Great Serpent Mound. However, charcoal from within the mound has been tested to later in history, around 1000 CE. Thus, the mound may have been built by the Fort Ancient peoples, who lived in the Ohio Valley from 1000 CE to 1550 CE.

The mound is located within the Serpent Mound State Memorial and has been designated a National Historic Landmark by the Department of Interior. The State maintains a museum near the Mound.