Inyo County is on the east side of the Sierra Nevada and southeast of Yosemite National Park in Central California. It contains the Owens River Valley; it is flanked to the west by the Sierra Nevada and to the east by the White Mountains and the Inyo Mountains. With an area of 10,192 square miles (26,397 km2), Inyo County is the second-largest county by area in California, after San Bernardino County. Almost one-half of that area is within Death Valley National Park. However, with a population density of 1.8 people per square mile, it also has the second lowest population density in California.

Mount Whitney, the highest peak in the Contiguous United States, is on Inyo County’s western border (with Tulare County). The Badwater Basin in Death Valley National Park, the lowest place in North America, is in eastern Inyo County. The difference between the two points is about 14,700 feet (4,500 m). They are not visible from each other, but both can be observed from the Panamint Range on the west side of Death Valley, above the Panamint Valley. Thus, Inyo County has the greatest elevation difference among all of the counties and county-equivalents in the contiguous United States.