It rises in a wet plateau of the island's central highlands, in the Alaka'i Swamp, the largest high-elevation swamp in the world. It flows south, passing through the spectactular 3,000-foot deep (900 m) Waimea Canyon, known as the "Grand Canyon of the Pacific."

The valleys of the Waimea River and its tributary, the Makaweli River, were once heavily populated. It enters the Pacific Ocean at Waimea, near the 1778 landing place of Captain Cook on Kauai.

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