As the sister city of Nekhen, Nekheb also played an important role during the earliest times of Egypt's history and in successive ages. The city enclosure rests across the Nile from Nekhen and is situated on the east bank, measuring approximately 550 meters by 550 meters and is surrounded by mud-brick walls. From at least the beginning of the 18th Dynasty onwards it replaced Nekhen and served as the capital of the Nome of the Shrine, but later relinquished this role to the city of Esna. Nekheb was also the home of the vulture goddess Nekhbet who, with the cobra goddess Wadjit of Buto, were the tutelary goddesses of Egyptian kings.

A visitor or resident walking through the streets of the city would have passed by breweries, kilns and bead-makers and the call of barbers advertising their services would have been part of the everyday sounds of the city. Holding a prominent position within the town enclosure would have been the main Temple of Nekhbet with its subsidiary structures, such as a birth house, smaller temples and a sacred lake. Nearby resides an extensive Predynastic cemetery, giving evidence of the longevity of Nekheb. Nobles and commoners alike would have built homes within the city walls and would have interacted on an almost daily basis either as servants to employers or merchants to customers.

Through the many dynasties several Pharaohs have built within Nekheb, from prior to the 2nd Dynasty onwards and during the 18th Dynasty major building activity started on the Temple of Nekhbet. Khasekhemwy, Mentuhotep, Thutmose III, Amenhotep II and Psammetichus I are only a few of the kings of Egypt to lavish attention upon Nekheb. Several "desert temples" were built in the vacinity of Nekheb and venerated such gods as Shesmetet, Re-Harakhty, Hathor and Amun. In addition to the Predynastic cemetery, rock cut tombs dating from the first half of the 18th Dynasty exist in the area, including the tomb of 'Ahmose, son of Ebana'. From the earliest times to the Ptolemiac Dynasty, Nekheb played an important role within the Nome of the Shrine commanding the attention of kings and playing home to one of the most important goddesses in Egypt.