Egypt, located on the Isthmus of Africa, is an ideal region to study historical population dynamics because of its geographic location and documented interactions with ancient civilizations in Africa, Asia and Europe. Particularly in the first millennium BC. Egypt struggled with foreign domination, which led to an increase in the number of foreigners living within its borders who could make genetic contributions to the local population. In this paper, we analyze the mtDNA and nuclear DNA of mummified humans recovered from Middle Egypt, covering some 1,300 years of ancient Egyptian history, from the Third Transitional Epoch to the Roman Period. Our analysis reveals that ancient Egyptians had more in common with Middle Eastern ancestry than modern Egyptians, who received additional sub-Saharan admixture in more recent times. This analysis establishes ancient Egyptian mummies as a genetic source for the study of ancient human history and offers the prospect of deciphering Egypt's past at the whole-genome level.