Ankhesenamon was the daughter of Akhenaten and Queen Nefertiti. She was originally called Ankhesenpa'aten and was thirteen years old when she became the queen of Tut'ankhamun when he was only eight years old. She was born in 'Amarna to the royal family. Tut'ankhamun succeeded Smenkhkare' in 1333 BC, but only ruled for 10 years.

When Tut'ankhamun died, Ankhesenamon took some drastic measures perhaps because she was afraid of the priests and the power of Horemhab, which was growing. Horemhab was stirring up opposition to 'Amarna and the worship of the god Aten. Ankhesenamon wrote to the king of the Hittites, King Suppiluliumash, who was an emerging power in the northern Mediterranean. She offered herself and the throne of Egypt to one of his sons. Prince Zannanza set out for Egypt, but was murdered on the border of Egypt. It is probable that he was killed by Horemhab's military agents.

The man chosen to succeed Tut'ankhamun was Aya, who was master of horse in Thebes. Ankhesenamon was given to Aya as his bride. Some believe that Aya was the father of Queen Nefertiti, which would have made him Ankhesenamon's grandfather. Together, they assumed the throne before Tut'ankhamun was buried. Aya died in 1319 BC, but Ankhesenamon disappeared before his death. She was replaced by Aya's wife, Tey.