The portion at Tioga Pass at Yosemite's eastern boundary is the highest paved through road in the California State Route system.

East of Oakdale there are no highly populated areas for 90 miles (144 km) as it heads into the foothills of the Sierra Nevada and into Yosemite National Park.

Both the portions through Yosemite National Park and the stretch between Mono Lake and Benton are subject to winter closure.

Usually the highway is open through Tioga Pass by the Memorial Day weekend at the end of May, and typically closes for the winter sometime in November.

NPS management wanted to "open up" the High Sierra section of the park to vastly increased numbers of visitors, and planned a new visitor center and other facilities at Tuolumne Meadows, as well as campgrounds and other facilities along the Tioga Road.

This brought fierce opposition from the Sierra Club, led by famed photographer Ansel Adams.

At the time, Sierra Club opposition created a serious rift in the long-time close relationship between the environmental organization and the National Park Service.

[23] Except where prefixed with a letter, postmiles were measured on the road as it was in 1964, based on the alignment that existed at the time, and do not necessarily reflect current mileage.