Despite the "0" as the last digit in the number, US 10 is no longer a cross-country highway, and it never was a full coast-to-coast route.

In 2015, the ferry SS Badger between Ludington, Michigan, and Manitowoc, Wisconsin, was officially designated as part of the highway.

The road enters Minnesota in Moorhead and travels through Detroit Lakes, Wadena, Staples, Little Falls, St.

It leaves US 61 just north of Hastings as a two-lane highway shortly before entering into Wisconsin.

US 10 enters Wisconsin at Prescott and travels southeastward passing Durand, Neillsville, Marshfield, Stevens Point, and Appleton before reaching its eastern terminus near the Lake Michigan shore in Manitowoc.

This allows travelers to bypass Hewitt, Auburndale, Blenker, Milladore, Junction City, and downtown Stevens Point.

The road then heads easterly through Baldwin and Reed City before it becomes a freeway west of US 127 near the junction with highway M-115.

routes were used, including one from Spokane to Missoula from 1941 to 1967 via Sandpoint, Idaho (represented today by US 2, State Highway 200, MT 200 and US 93), and the Pintler Scenic Route through Philipsburg, and Anaconda, renamed MT 1 when Montana's US 10 was decommissioned in 1986.

[10] US 10N through Helena and dropping into Three Forks, while the Southern section of the split followed US 10's traditional routing through Deer Lodge and Butte, Montana, to get across the Rocky Mountains.

[12] At the eastern end, US 10 originally went south from Midland to Saginaw, Michigan, on what is now highway M-47.

[8] In the 1970s, US 10 was rerouted off Woodward Avenue in Metro Detroit and onto the John C. Lodge Freeway (formerly Business Spur 696, now M-10) and Telegraph Road.

A multistate alternate route between Washington and Montana was largely replaced in 1947 by the western extension of US 2 and later decommissioned entirely in 1967.