Cottonwood Creek originates in the Ancient Bristlecone Pine Forests of the White Mountains of eastern California. The creek flows eastward from below the alpine crest of the White Mountains and descends through groves of bristlecone pine, aspen and mountain mahogany, then a woodland of pinyon pine and juniper, and finally into sagebrush as the stream ends in endorheic Fish Lake Valley which is one of the contiguous collection of inward-draining basins that make up the Great Basin.