It is not known when Qatna lost its independence. It became a Mitannian vassal in the 16th century BC, but the archive of Qatna proves that even in its final period during the 14th century BC, Qatna maintained a certain degree of autonomy. Early Egyptian military intrusions to the region occurred under Thutmose I (). The name Qedem appears in an inscription found on a fragmented gateway from Karnak dated to the reign of Thutmose mentioning a military campaign in the northern Levant. The inscription suggests that the mentioned cities submitted to the king. The geographic sequence given in the inscription is Qedem ("Qdm"), Tunip ("Twnjp") and "Ḏj3 wny" (maybe Siyannu); Qatna (Qdn in Egyptian) would fit better in the geographic sequence and Alexander Ahrens suggested that the inscription might have meant Qatna. Any oaths of loyalty to Egypt taken by Levantine rulers were forgotten after Thutmose I's death. The Egyptians returned under the leadership of Thutmose III (), who reached Qatna during his eighth Asiatic campaign, . Thutmose III did not rule directly in Qatna but established vassalage ties and attended an archery contest with the Qaṭanean king.