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The name Mekong is an English and French approximation of the Thai and Lao Mae Khong — Mae meaning 'mother' or 'great river,' and Khong deriving from an older word, possibly from Khmer kong (river) or from a Mon-Khmer root for water. The river itself flows from the Tibetan Plateau through China's Yunnan province, then through Myanmar, Laos, Thailand, Cambodia, and Vietnam before emptying into the South China Sea through a vast delta. It is the twelfth longest river in the world and the seventh longest in Asia. Each country it passes through gives it a different name.

In Chinese, the river is known as the Lancang Jiang (澜沧江) — 'turbulent blue river' — in its upper reaches. In Khmer, it is called Tonle Thom (Great Water) in certain stretches, and in Vietnamese its delta section carries the name Cửu Long — 'Nine Dragons' — for the nine channels through which it reaches the sea. None of these names are translations of each other; each reflects the perspective of those who live on a particular bank, in a particular culture, at a particular moment of the river's character. The river changes as it flows, and so do its names.

European contact with the Mekong began through Portuguese missionaries and traders in the sixteenth century, but systematic exploration came with the French Mekong Expedition of 1866–1868, led by Francis Garnier and Ernest Doudart de Lagrée. The French transcribed the Thai-Lao Mae Khong as 'Mékong,' and this spelling entered European cartography and eventually English usage as 'Mekong.' The French name imposed a colonial standardization on a word that had belonged to many communities with many pronunciations.

The Mekong Basin today is one of the most biologically diverse river systems on Earth, supporting the largest inland fishery in the world and tens of millions of people who depend on its annual flood-pulse for rice cultivation. The word Mekong has become global shorthand for Southeast Asian river culture, the Great River that defies any single nation's claim. In the twenty-first century, upstream dams in China and Laos have altered the river's flow, and the word Mekong has entered environmental discourse as a symbol of contested water rights and transboundary ecology.