Amenhotep inherited a vast kingdom from his father Thutmose III, and held it by means of a few military campaigns in Syria; however, he fought much less than his father, and his reign saw the effective cessation of hostilities between Egypt and Mitanni, the major kingdoms vying for power in Syria.
Amenhotep je naslijedio prostrano kraljevtsvo od svog oca Thutmozisa III te ga održavao kroz nekoliko vojnih pohoda na Siriju; međutim, mnogo manje se borio od svog oca, a za vladavine je došlo do praktičnog završetka neprijateljstava između Egipta i države Mitanni, glavnog egipatskog suparnika za prevlast u Siriji.