Thutmose I was born into the early Eighteenth Dynasty, the dynasty that had expelled the Hyksos, the foreign rulers who had dominated the Delta for more than a century, and reunified Egypt under native kings. His mother was Seniseneb, a woman of non-royal birth who may have been a minor wife or concubine of Amenhotep I, the second pharaoh of the dynasty, though some scholars believe Thutmose I was Amenhotep I's son while others suggest he was a military commander who married into the royal family to secure his claim. What is certain is that he was not born to be king. He earned the throne through ability, and he kept it through conquest.

His marriage to Ahmose was the key to his legitimacy. Ahmose was the daughter of Ahmose I, the founder of the dynasty who had driven the Hyksos from Egypt, and of Ahmose-Nefertari, the Great Royal Wife whose cult would endure for centuries. Some sources suggest Ahmose was also the sister of Amenhotep I, which would make her Thutmose I's aunt as well as his wife, a relationship that the Egyptians would have found entirely proper for a divine king. By marrying Ahmose, Thutmose I connected himself to the bloodline of the dynasty's founder and secured the throne for his children. She bore him at least two children who would shape the future of Egypt: Thutmose II, the son who would succeed him, and Hatshepsut, the daughter who would become the most powerful woman in Egyptian history. By a secondary wife named Mutnofret, he also fathered Amenmose, Wadjmose, and possibly Ramose, princes who would not live to rule.

The defining military achievement of Thutmose I's reign came in his second year, when he led a river expedition into Nubia, the land south of Elephantine where the Nile narrowed between granite cliffs and the desert kingdom of Kush had long resisted Egyptian control. The campaign was recorded on the Tombos Stela, a rock inscription carved on a boulder at Tombos near the Third Cataract of the Nile. The text, written in the bombastic poetry of royal propaganda, declares that the pharaoh overthrew the chief of the Nubians, that no escape existed among the evil-of-character, and that the stench of the fallen flooded their wadis. According to the tomb autobiography of Ahmose, son of Abana, a soldier who served in the campaign, Thutmose I personally killed the Nubian king in battle, a feat of arms that no pharaoh had claimed for generations. But Thutmose did not stop at the Third Cataract. He pushed further south, past the Fourth Cataract to a place called Kurgus, where the Nile does something extraordinary: the river changes direction and appears to flow upstream while going downstream, a phenomenon that confused Egyptian sailors and that the Tombos Stela describes as the inverted water. He set up boundary markers, appointed a viceroy to govern Nubia in the king's name, and returned to Egypt after seventeen months of campaigning, having extended the southern frontier farther than any pharaoh before him.

Then he turned north. In his fourth or fifth regnal year, Thutmose I led an army into Syria, pursuing the remnants of Hyksos influence and the petty kingdoms of the Levant that had never acknowledged Egyptian sovereignty. He reached the Euphrates River near Carchemish, in what is now southern Turkey, and carved a stela on its banks declaring the river his northern border. He was the first king of Egypt to cross the Euphrates, a feat that even the great conquerors of the Middle Kingdom had not achieved. The campaign was not merely a raid. It was a statement that Egypt was now an imperial power, not merely a kingdom defending its borders but an empire projecting force across the known world.

At home, Thutmose I was an equally ambitious builder. He transformed the temple of Amun at Karnak from a modest Middle Kingdom complex into the greatest religious centre in Egypt. He erected the fifth pylon and an enclosure wall around the inner sanctuary, then built a fourth pylon and another wall beyond it, creating the axial design - a straight processional way flanked by pylons and courts - that would become the standard for every New Kingdom temple after him. Between the fourth and fifth pylons he constructed a hypostyle hall with columns of cedar wood imported from Lebanon, and along its edges he placed colossal statues of himself, alternating between the white crown of Upper Egypt and the red crown of Lower Egypt. In front of the fourth pylon he raised two obelisks of red granite, one of which would not be inscribed until his grandson Thutmose III added his own titulary fifty years later. The architect who supervised all this was Ineni, a man whose tomb autobiography records that he dug the king's tomb and built his temple, though the mortuary temple itself has never been found, possibly because Hatshepsut later demolished or incorporated it into her own temple at Deir el-Bahri.

The most enduring innovation of Thutmose I's reign was his choice of burial place. Before him, pharaohs had been buried in pyramids or in rock-cut tombs at various sites, but Thutmose I chose a new location: a secluded valley in the cliffs west of Thebes, hidden from view and accessible only by a narrow path. This was the Valley of the Kings, and his tomb, KV20, was the first royal tomb to be cut there. The tomb was quarried in a curving, clockwise plan that descended deep into the bedrock, and it was later extended by his daughter Hatshepsut so that she could be buried beside him. But Thutmose I was not destined to rest peacefully in his original tomb. His grandson Thutmose III, who resented Hatshepsut's usurpation of his throne, moved the old king's body to a new tomb, KV38, which he had prepared for his grandfather, and there the mummy lay until the Twenty-first Dynasty priests, seeking to protect royal bodies from tomb robbers, gathered them into a hidden cache at Deir el-Bahri. The mummy of Thutmose I was discovered in this cache in 1881, wrapped in coffins that Thutmose III had prepared for him, and though the body was damaged by ancient robbers who had hacked at the face and chest, the features still suggested a man of determination and vigour.

Thutmose I died after a reign of approximately thirteen years, around 1493 BCE, and was succeeded by his son Thutmose II, a sickly youth who married his half-sister Hatshepsut and ruled for only a few years before his own early death. Thutmose II's son, Thutmose III, was still a child when he ascended the throne, and Hatshepsut seized power as regent and then as pharaoh, ruling for more than two decades before Thutmose III finally came into his own and became the greatest conqueror in Egyptian history. Every one of Thutmose III's campaigns, from the plains of Megiddo to the banks of the Euphrates, followed the path that Thutmose I had blazed. The empire that Thutmose III would make the greatest in the ancient world was founded by his grandfather's sword.