In the 20th or 21st year of Hatshepsut's reign, Thutmosis III took over the throne for himself solely.
At the end of about 17 years of military campaigns, Thutmosis III had successfully established Egyptian dominance over Palestine, and had made strong inroads into Southern Syria. His own reputation was assured.
The face of Thutmosis III on his statues continued the 'Thutmoside' profile seen already with Thutmosis I. He did not dishonor the name and monuments of Hatshepsut until the last years of his reign.
Thutmosis III used his 32 years of sole rule to make his name prominent throughout Egypt and Nubia. He was active at Gebel Barkal at the farthest southern point in Nubia, at Sai, at the Third Cataract, Semna, Kumma, Uronarti, Buhen, Quban, Amada, Faras, as well as several other locations where blocks are known in his name. Further North, his monuments are well attested at Elephantine, where he built a temple honoring Goddess Satet of the First Cataract Region, at Kom Ombo, Edfu, EI-Kab, Tod, Armant, Thebes, Akhmim, Hermopolis, and Heliopolis. A statue of the Overseer of Works, Minmose, active in the later reign of Thutmosis III, listed cult sites at which he worked. He named, in addition to the places already mentioned, Medamud, Asyut, Atfih, and a number of localities in the Delta, including Buto and Busiris.
It is not certain that the three wives of Thutmosis III buried in Wadi Gubbanet el-Qirud (in Western Thebes) were Syrian, but their names were certainly Asiatic. Thutmosis III's wives included one woman called Sitiah, daughter of a royal nurse. If she in fact replaced Neferure in the priestess' position, it was only until Thutmosis III's daughter Merytamun was old enough to take up the role. Sitiah is not definitely known to have had any children, while the mother of Amenhotep II, Merytre, appears to have produced several children. Merytre (daughter of Huy) apparently gave birth to Amenhotep, Princess Merytamun, Prince Menkheperre, Princesses Isis and another Merytamun, and a small princess Nebetiunet. Merytre as queen appeared in the temple of Medinet Habu and in the Tomb of Thutmosis III. A third wife, Nebtta, and a princess Nefertiry are depicted in the royal tomb.
The Tomb of Thutmosis III in the Valley of the Kings (KV 34) was cut high in a cliff. The walls of the burial chamber are covered with hieratic form of the Netherworld texts: the Litany of Re, which calls upon the names of the Sun-god to aid the king in his afterlife journeys, and the Book of what is in the Netherworld (Amduat), which provided the king with a map of the underworld and spells to help him achieve eternal justification.