Music was ubiquitous throughout Mesopotamian history, playing important roles in both religious and secular contexts. Mesopotamia is of particular interest to scholars because evidence from the region—which includes artifacts, artistic depictions, and written records—places it among the earliest well-documented cultures in the history of music. The discovery of a bone wind instrument dating to the 5th millennium BCE provides the earliest evidence of music culture in Mesopotamia; depictions of music and musicians appear in the 4th millennium BCE; and later, in the city of Uruk, the pictograms for 'harp' and 'musician' are present among the earliest known examples of writing.

Music played a central role in Mesopotamian religion and some instruments themselves were regarded as minor deities and given proper names, such as Ninigizibara. Its use in secular occasions included festivals, warfare, and funerals—among all classes of society. Mesopotamians sang and played percussion, wind, and string instruments; instructions for playing them were discovered on clay tablets. Surviving artifacts include the oldest known string instruments, the Lyres of Ur, which includes the Bull Headed Lyre of Ur.

There are several surviving works of written music; the Hurrian songs, particularly the "Hymn to Nikkal", represent the oldest known substantially complete notated music. Modern scholars have attempted to recreate the melodies from these works, although there is no consensus on exactly how the music would have sounded. The Mesopotamians had an elaborate system of music theory and some level of music education. Music in Mesopotamia influenced, and was influenced by, music in neighboring cultures of antiquity based in Egypt, East and West Africa, and the Mediterranean coast.

Much of what researchers know about Mesopotamian music comes from clay tablets. Scribes would use a reed stylus to make wedge-shaped impressions in wet clay, and the tablets would be baked. Using this cuneiform script, they recorded texts that listed genres and song titles, included instructions on how to play instruments, and articulated their music theory. By piecing together thousands of surviving tablets, as well as examining surviving artworks and instruments, researchers have been able to offer a detailed picture of Mesopotamian music culture.

Music played a central role in ancient Mesopotamian religion. In the Old Babylonian period (c. 1894 BCE – c. 1595 BCE), when music was performed as part of a religious ceremony, the practitioners, known in Sumerian as gala priests, sang in a dialect of Sumerian called Emesal. There were two types of Emesal prayers, the Balag and the Ershemma, named after the instruments used in their performance (the balag and shem, respectively). In some depictions of religious festivals, musicians were accompanied by dancers, jugglers, and acrobats.

Evidence from the city of Mari offers a picture of how the musicians were situated within the temple. An instrument called Ninigizibara was placed opposite a statue of that city's deity, Eštar. Singers sat to the right of the instrument, an orchestra sat to its left, and female musicians stood behind the instrument. Ritual acts were performed during these sung lamentation prayers, whose purpose was to persuade the local deity not to abandon the city. Moreover, some laments included grief over the loss of music itself during the destruction of a city and its temple. In one such work, the "weeping goddess" Ninisinna laments the destruction of her city, Isin, not only bemoaning the loss of food, drink, and luxury, but also because there were "no sweet-sounding musical instruments such as the lyre, drum, tambourine, and reed pipe; no comforting songs and soothing words from the temple singers and priests".

Some rituals involved the instruments themselves, deified, and capable of receiving animal sacrifices as gods. In a ritual closely associated with a drum described in an Akkadian text, a bull was brought to the temple and offerings were made to Ea, god of music and wisdom. Various parts of the bull were burned with a torch during the ritual. Twelve linens were placed on the ground, and a bronze image of a god was placed on top of each linen. Sacrifices were made and a drum was put into place. The bronze images were then put inside the drum, incantations were whispered into the bull's ears, a hymn was sung accompanied by an oboe, and the bull was sacrificed.

The Akkadian word for music, nigūtu, also meant 'joy' and 'merriment', well illustrated by a seal in the Louvre showing a peaceful scene of a shepherd playing a flute to his flock. Music was a normal part of social life in Mesopotamia and was used in many secular contexts. Music played important roles at funerals, among royalty, and was also depicted in relation to sports and sex. Mesopotamian love songs, which represented a distinct genre of music, nevertheless shared features in common with religious music. Inana and Dumuzi, often featured in laments, are also prominent as the divine lovers in romantic songs, and both genres used Emesal, a dialect associated with women. The use of Emesal by women singers extended into wedding songs as well, but over time these singing roles were taken over by male performers, at least among the elite. In the Early Dynastic III period, music was depicted at banquets, but the purpose is unclear. The celebration may have been "a regular calendrical event, such as the New Year's festival" or the occasions may have been "extensions of temple practices or celebrations of successful military campaigns".