In this study, the evolution of instruments in Ancient Mesopotamian and Anatolian cultures was examined starting from the Sumerians up to the Hittite civilization. The instruments as high-ranking cultural assets are not only simple instruments in which sound, loudness, timbre, sound intensity are generated. They are the indispensable elements of rituals, conversation, communication, and more importantly art in Mesopotamia and Anatolia. The importance of instruments as high-ranking cultural assets in the Sumerian period (BC) is proven by the numerous classifications made. Cuneiform script originating from Mesopotamia has been an important type of script spreading out from Asia Minor, used in the writing of various languages from different groups and the most important source in revealing the information about the music and instrument culture of the period was undoubtedly the texts written in cuneiform, as well as the instrument finds and pictorial descriptions. Cuneiform texts give us instrument names rather than instrument types. The lexical (glossary) lists, which are available in two languages, Sumerian-Akkadian, which sometimes include descriptions of instruments, give us the Sumerian and Akkadian names of the instruments. In some cases, besides the instrument names, there are certain clues with occasional addendums regarding the material from which the instrument is made. The most important of the Mesopotamian civilizations, which started to form in the early period in the 12.000 B.C., are respectively; Sumerian, Akkad, Babylonian, Assyrian and Hittite civilizations. The cultural experiences of each of these civilizations naturally transferred influences from their cultures to the next society.