The route is known for being the highway on which actor James Dean died in a car accident on September 30, 1955, at the intersection of CA 41 near Cholame, California.

US 466 began in Morro Bay, continuing to US 101 before turning north and following the path of today's SR 41 to Shandon in San Luis Obispo County.

From the Nevada state line on Hoover Dam, U.S. Route 466 remained co-signed with US 93 as it headed southeast.

The highway was also the eastern terminus of SR 68 at Coyote Pass, which headed west towards Bullhead City and Laughlin, Nevada.

[2] On October 9, 1933, the American Association of State Highway Officials (AASHO) approved an extension of US 466 from Barstow to US 66 in Kingman, Arizona.

[8] On December 3, 1971, AASHTO approved a request from Arizona and Nevada to remove the US 466 entirely from both states, after which, the US 466 designation ceased to exist.