Mut did not begin as the wife of Amun. She was an independent goddess with her own temples and priesthood long before the Theban god rose to national prominence, and her name appears in texts from the Middle Kingdom around 2055 BCE, though her origins may stretch even further back into the shadows of Egyptian prehistory. In the earliest centuries she was worshipped as a local deity, a mother goddess associated with the vulture, which the Egyptians observed protecting its young with fierce devotion. Her very name, mwt, was also the word for vulture, and the two ideas were inseparable in the Egyptian mind: to be a mother was to be a vulture, and to be a vulture was to be a mother. She wore the vulture headdress that marked queens and great goddesses, and upon that headdress she placed the double crown of Egypt, the Pschent, combining the white crown of Upper Egypt and the red crown of Lower Egypt into a single symbol of universal dominion. No other goddess in Egypt wore this crown so consistently, and it announced to every viewer that Mut was not merely a consort but a sovereign in her own right.

Her rise to power came with the rise of Thebes. When the pharaohs of the Eleventh and Twelfth Dynasties made Thebes their capital, they elevated their local god Amun from a minor deity of the air to a national force, and when Amun merged with Ra, the great sun god, to become Amun-Ra, the king of the gods, Mut became his queen. Their son was originally Montu, the falcon-headed war god of Thebes, but by the New Kingdom he had been replaced by Khonsu, the youthful moon god who travelled across the night sky and governed time, healing, and fertility. The three of them formed the Theban Triad, and their worship became the state religion of Egypt during its most glorious centuries. Pharaohs claimed to be the divine children of Amun and Mut, and queens like Hatshepsut, the female pharaoh of the Eighteenth Dynasty, and Nefertari Merytnmut, the chief wife of Ramesses II, bore her name in their own titles and dedicated temples and statues to her honour.

The greatest myth of Mut is the tale of the Wandering Eye, recorded in the Demotic Papyrus of Leiden from the Ptolemaic period. In this story, Ra the sun god grew angry with the world and sent his Eye, the fierce feminine aspect of his own power, to punish the rebels. The Eye took the form of a lioness and fled Egypt, wandering south into the lands beyond the Nile as a wild cat filled with rage. Ra, seeing the devastation she left behind, sent Thoth, the ibis-headed god of wisdom and writing, to persuade her to return. Thoth approached her in the form of a baboon and calmed her with stories and songs, reminding her of her homeland, her twin brother Shu, the god of air, and the temple of her father at Thebes. Slowly her anger cooled, and she transformed into a vulture and flew north toward Egypt. She landed at Elkab, the ancient vulture city, and then changed into a gazelle as she approached Thebes. But followers of Apep, the serpent of chaos who attacks the sun boat each night, ambushed her near the city. Thoth warned her, and together they escaped by boat, hiding in the reeds until they reached the safety of the temple precinct. There she resumed her divine form and was welcomed as Mut, the great mother who had returned to her city, and in some versions she then transformed into Hathor, the golden cow goddess of love and music, to be fully reconciled with her father Ra. This myth explained why Mut was both the Eye of Ra and the mother of the sun: she was the daughter who became the mother, the wanderer who came home.

Mut's temple at Karnak was one of the most important religious sites in Egypt. Called Hwt-Mwt, the Estate of Mut, it stood immediately south of the great temple of Amun-Ra and was approached by an avenue of sphinxes. The precinct was dominated by a crescent-shaped sacred lake called the Isheru, whose curved form mirrored the shape of the moon and provided a symbolic setting for the goddess's rituals. Within the temple, Mut was worshipped as "Mut, the Great Lady of Isheru, the Lady of Heaven, the Queen of the Gods," and her statue was carried in procession around the lake during the annual Festival of Mut, when priests sang hymns and offered incense to celebrate her return and renewal. The temple also housed hundreds of statues of Sekhmet, the lion-headed goddess of war and plague, which had been moved from the funerary temple of Amenhotep III on the west bank of the Nile. These statues stood in rows throughout the precinct, their granite faces stern and unblinking, a reminder that Mut contained within herself both the nurturing vulture and the destroying lioness.

During the Opet Festival, the most important celebration in the Theban calendar, the sacred barques of Amun, Mut, and Khonsu were carried from Karnak to the Luxor Temple along an avenue of sphinxes nearly three kilometres long. The procession was accompanied by chanting priests, dancers, and musicians, and at Luxor the image of Amun was ceremonially united with Mut, a symbolic renewal of divine kingship and cosmic fertility that ensured the continued prosperity of Egypt. The festival was held during the inundation season, when the Nile flooded its banks and brought new life to the land, and the union of Amun and Mut mirrored the union of the river and the earth. Even after the New Kingdom ended and Thebes lost its political power, the cult of Mut endured. The Nubian and Kushite rulers of the Twenty-Fifth Dynasty restored her temple and claimed descent from the Theban Triad, and the Ptolemies and Romans continued to honour her at Karnak until the old temples were finally closed in the early centuries of the Common Era.