It runs westwards from Beijing via Datong, Yinchuan and Xining to Golmud before turning southwest to Lhasa.

The section of the highway within western Qinghai and Tibet, from Golmud to Lhasa, is paralleled by the Qinghai-Tibet Railway.

The highway reaches its highest elevation of 5,231 meters (17,162 ft) at Tanggula Pass.

Since it was opened to traffic in 1954, the central government has spent nearly 3 billion yuan (US$362 million) on three major overhauls.

Another extension plan was announced in 2022, including new small purpose connection highways (601-701).