With two-thirds of its length in Boise County, it passes by historic Idaho City and the village of Lowman to the western edge of the Sawtooth Mountains, then along their northern boundary to Stanley.

The road is designated as one of Idaho's scenic byways and provides access to Sawtooth National Recreation Area from Boise and the Treasure Valley.

At "Cape Horn" the highway turns southeast to gradually climb with Marsh Creek to the border of the Sawtooth National Recreation Area, where SH-21 enters the drainage of the main Salmon River, and gently descends to Stanley.

[citation needed] In Stanley, SH-21 terminates at 6,250 feet (1,905 m) at the junction with SH-75, the Sawtooth Scenic Byway from Galena Summit and Ketchum to the south, originating in Shoshone.

[citation needed] Portions of the highway originated in the 1860s, as a toll road connecting Boise with the gold mining areas near Idaho City.

[11][12] The realigned SH-21 would also serve an expanded Micron Technology facility and residential development on land owned by the J.R. Simplot Company.