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The Serapeum, dedicated to the sacred Apis bull, is one of the highlights of visiting Saqqara. The first Apis burial took place in the reign of Amenhotep III (1390–1352 BC), and the practice continued until 30 BC. The enormous granite and limestone coffins weighed up to 80 tonnes each. When it died, the bull was mummified at Memphis, then carried in a stately procession to the Serapeum's subterranean galleries and placed in a huge stone sarcophagus.

The Apis, it was believed, was an incarnation of Ptah, the god of Memphis, and was the calf of a cow struck by lightning from heaven. The Apis bulls were by far the most important of the cult animals entombed at Saqqara. Once divinely impregnated, the cow could never again give birth, and her calf was kept in the Temple of Ptah at Memphis and worshipped as a god. The Apis was always portrayed as black, with a distinctive white diamond on its forehead, the image of a vulture on its back and a scarab-shaped mark on its tongue.

Until the mid-19th century, the existence of the sacred Apis tombs was known only from classical references. In 1851, Auguste Mariette, after finding a half-buried sphinx at Saqqara, and using the description given by the Greek historian Strabo in 24 BC, uncovered the avenue leading to the Serapeum. However, only one Apis sarcophagus was found intact.