Its northern terminus is at the Canadian border in Eastport, Idaho, where the roadway continues north as British Columbia Highway 95.

Here, it merges with I-10 and runs concurrent, heading westward for 17 miles (27 km) until the Colorado River, where it enters California, just shy of Blythe.

It joins at the interchange as a multi-lane divided freeway past SR 173 and as part of the concurrent route of I-11 and US 93 in Boulder City.

US 95 continues as a freeway until again becoming a divided highway at Corn Creek Road, where I-11 temporarily ends, northwest of the Las Vegas Valley.

In Oregon, US 95 is an undivided two-lane highway in the sparsely-populated high desert in the southeastern corner of the state, running completely in rural Malheur County.

From the Nevada state line at McDermitt, the highway heads north and gradually climbs to its crest at Blue Mountain Pass, at an elevation of 5,293 feet (1,613 m) above sea level.

The highway heads north-northeastward to the Idaho state line, entering southwest of Marsing in Owyhee County.

The highways split as US 12 continues west to Lewiston, and US 95 turns northwest and climbs a steep grade up to the rolling Palouse.

[6] When the plan was adopted by the American Association of State Highway Transportation Officials on November 11, 1926, the route of US 95 had been approved south to Weiser, still existing solely in Idaho.

[7] A proposal to extend US 95 south to Winnemucca, Nevada, was considered by AASHO in 1937; however, action was deferred due to sections in Oregon that were incomplete.

AASHTO reconsidered the idea at its meeting on June 28, 1939, as part of a larger plan to extend the highway south to Blythe, California.

[7] On June 27, 1960, US 95 was extended further south into Arizona, through Yuma to the Mexican border in San Luis, which still serves as the southern terminus of US 95.

The first stage was completed in August 2005 from just south of Coeur d'Alene to Fighting Creek Road, and is an upgraded four-lane highway for approximately ten miles (16 km).

The interstate highway would primarily follow the US 95 corridor through central and northwestern Nevada, extending to I-80 near Reno and Sparks via Tonopah.

In 2018, the Nevada Department of Transportation had initiated public outreach regarding its long-range planning efforts to narrow down options for the future I-11 corridor.