He was the son of Pharaoh Thutmose II and Isis, a minor wife. When Thutmose II died in 1504 BC, Thutmose III became ruler. However, he shared the beginning of his reign with Hatshepsut, his father's wife, who acted as regent and eventually co-ruler. For approximately 22 years Thutmose III had little power over the empire. He married Hatshepsut's youngest daughter, Meritre, with whom he had a son named Ahmose II. At some point, however, Hatshepsut disappears from the historical record and Thutmose III ruled by himself until his death in 1427 BC (some sources list his death ranging from 1425 BC to 1430 BC).
He was an active expansionist ruler, sometimes referred to as the "Napoleon of Egypt", because he was recorded to have conquered 350 cities during his rule, conquering much of the Near East.
His tomb in the Valley of the Kings is the first in which we find the complete Amduat, an important New Kingdom Ancient Egyptian funerary text.