Sekhmet was the lion-headed goddess, the daughter of Ra, the consort of Ptah at Memphis, the personification of the destroying power of the sun's heat and of the violence of plague and war. Her name signified "the Powerful"; she was depicted as a woman with the head of a lioness, crowned with the solar disk and the uraeus serpent. She was the active and angry aspect of the divine feminine — the Eye of Ra in its destroying form — and she was both feared and propitiated.

The great myth attached to her was the Destruction of Mankind, told already in the entry on Ra. Mankind had rebelled against the aging Ra, and Hathor was sent to punish them; Hathor in her descent became Sekhmet, and her killing went beyond instructions. The fields ran with blood; the goddess waded in human gore. To stop her, Ra brewed seven thousand jars of beer, dyed it red with ochre, and poured it across the fields where she would pass at dawn; she drank it, mistaking it for blood, and was lulled into a stupor; and so mankind was preserved. The festival of drunkenness at Dendera (mentioned in the entry on Hathor) commemorated this event each year, with the priestesses of Sekhmet drinking ritual red beer to symbolize the goddess's pacification.

Plague was particularly her province; the "arrows of Sekhmet" were the fevers and pestilences that struck individuals and populations alike. To avert her wrath, the Egyptian priesthood maintained an elaborate cult — the priests of Sekhmet were also physicians, and her temples preserved medical and pharmaceutical knowledge — and the New Kingdom king Amenhotep III installed in the Mut precinct at Karnak some six hundred granodiorite statues of Sekhmet, presumably to assist in averting the plague that troubled his late reign. The statues survived the millennia; many now stand in the world's great museums, an installation of imperial scale unmatched until modern times.