It follows a westward route into Kanagawa Prefecture, passing through the city of Sagamihara and one town.

In Nagano Prefecture, National Route 20 passes through five cities and towns before entering Shiojiri, where it terminates at the intersection of National Routes 19 and 153.

[2] National Route 20 is the successor to the Kōshū Kaidō, an Edo period highway connecting the shogunal capital of Edo and Kofu, then the principal city in Kai Province (or Kōshū, as it was also known).

The highway's course passes the Sakurada Gate of the Tokyo Imperial Palace.

The marathon course of the Tokyo Olympics included parts of National Route 20.