After reaching Shephard Avenue at the northeast edge of Clovis, it becomes the two-lane Tollhouse Road before it begins its ascent up the Sierra Foothills.

This rural mountain road runs east to the town of Bishop, then joins U.S. Route 395 for 14.6 miles, and separates from 395 in Big Pine.

The segment of the highway from Lake Sabrina east to the community of Aspendell is subject to closure to most vehicles during the winter months, usually not opening until mid- or late-April, due to snow removal.

[10][11] The eastern part of the route, from the eastern over Westgard Pass to the Nevada state line near Lida, Nevada predates the era of numbered highways and dates to the auto trail era as part of the Midland Trail, one of the earliest transcontinental roads in the USA.

It was at Big Pine that the Midland trail forked in its westward journey to its eventual western termini, Los Angeles and San Francisco.

The western descent from Westgard Pass into the Owens Valley was described as a "Welcome to California" view in the route guides for the Midland trail.

[15] 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.