US 395 enters Nevada in Topaz Lake as a two-lane highway and gradually winds its way to Carson Valley where it becomes the principal thoroughfare for the Gardnerville–Minden area.

US 50 departs from the freeway at East William Street, while I-580 and US 395 continue north through Carson City.

Upon entering Reno, the route is designated, since 1998, as the Martin Luther King Jr. Freeway.

Shortly afterward, US 395 turns northwest to serve the northern valleys of the Reno area before crossing back to California at the unincorporated Nevada community of Bordertown, in Cold Springs, Washoe County.

[4] The routing for I-580 and US 395 had been considered as a potential alignment for the extension of I-11 from US 95 north of Walker Lake to I-80 at the Spaghetti Bowl interchange in Reno.