Lost River begins and ends in a closed basin in northern California and southern Oregon in the United States. The river, 60 miles (97 km) long, flows in an arc from Clear Lake Reservoir in Modoc County, California, through Klamath County, Oregon, to Tule Lake in Siskiyou County, California. About 46 mi (74 km) of Lost River are in Oregon, and 14 miles (23 km) are in California.

The Klamath River flows 257 miles (414 km) through Oregon and northern California in the United States, emptying into the Pacific Ocean. By average discharge, the Klamath is the second largest river in California after the Sacramento River. Its nearly 16,000-square-mile (41,000 km2) watershed stretches from the high desert of south-central Oregon to the temperate rainforest of the North Coast. Unlike most rivers, the Klamath begins in a desert region and flows through the rugged Cascade Range and Klamath Mountains before reaching the ocean; National Geographic magazine has called the Klamath "a river upside down".