Tuthmosis was the king for only six years, but in that time he built a huge reputation as a mighty pharaoh. He led a legendary military expedition into Nubia, where he killed their chief in hand-to-hand combat. Legend says he returned to Egypt with the body of the chief hanging from his ship. Tuthmosis appointed a viceroy to manage Nubia and maintained a military presence there by building fortresses along the river.

He also wanted to serve up some revenge to the Hyksos for invading Egypt in the Second Intermediate Period, so he led an army all the way to the Euphrates River in Mesopotamia, taking out Hyksos tribes all along the way.

Tuthmosis began many building projects with the help of his architect Ineni. One such project was his extensive remodeling of the Temple of Amun at Karnak. Pylons, statues, and courtyards were added in his name.

Despite all the glory, Tuthmosis was just a regular military guy who married into the dynasty by taking the daughter of Ahmose I as his main queen. They had three children of "pure" royal blood: two sons (Wadjmose and Amenmose) and a daughter (Hatshepsut). Another son, Tuthmosis II, was born to a lesser wife so he was only half as royal as his sister and brothers.

During the New Kingdom, royal tombs were built high in the cliffs of Upper Egypt in a spot commonly called "The Valley of the Kings." In fact, Tuthmosis was the very first king to be buried there. The intention was to make the tombs as inaccessible to grave robbers as possible... although they got robbed anyway. Around 1000 BC, a group of priests gathered up all the royal mummies and stored them in two secret "mummy caches" (one near Deir el-Bahari, and the other in the tomb of Amenhotep II) to keep them safe. These hidden royals were nowhere to be found for almost 2,000 years: in 1881, the 40 mummies in the Deir el-Bahari location were found; then in 1898 the tomb of Amenhotep II with its additional 16 mummies was discovered. Tuthmosis I was in the 1881 cache.

Tuthmosis I appears to have two tombs in the Valley of the Kings. Egyptologists refer to his original tomb as KV20 which means "Tomb #20 in the Kings Valley." His daughter Hatshepsut joined him in KV20 many years later. Tuthmosis III (grandson of Tuthmosis I and step-son of Hatshepsut) built him a new tomb (KV38) because he didn't like the idea of his hated step-mother resting in his grandfather's tomb one bit!