It runs through the heart of the San Joaquin Valley from State Route 33 in Mendota through Fresno, and then east towards the Sierra Nevada to Kings Canyon National Park.

Nearly the entire 24-mile (39 km) stretch from the Kings River crossing to Cedar Grove is eligible for the State Scenic Highway System, and nearly the entire route from Paicines to Cedar Grove is part of the California Freeway and Expressway System.

The road no longer connects with its freeway bypass at all; the east and west ends terminate in cul-de-sacs.

It follows the Kings River into General Grant Grove, where SR 198 splits off south toward Sequoia National Park.

At the entrance of Kings Canyon National Park, SR 180 legally ends but the road continues east through Cedar Grove to a dead-end in Kanawyers.

A 24-mile (39 km) length east of unbuilt State Route 65 near Minkler to the boundary of Kings Canyon, excepting the 2-mile (3.2 km) portion through General Grant Grove, is eligible for the State Scenic Highway System;[9] most of this segment was officially designated as a scenic highway by the California Department of Transportation in 2016.

[4] A study into the use of Measure C funds found that traffic volumes will likely increase between 50% and 100% across the entire road by 2020, especially in the more rural areas.

[16] In 1905, the easternmost portion of what is now SR 180 was created as Legislative Route 41, from General Grant Grove to the Kings River Canyon; in 1919, a bond measure funded the extension and upgrade to Fresno, which was completed by 1933.

The Stanislaus and Tuolumne bridges were built in 1958 to alleviate congestion at the train tracks and local industry,[18] and when US 99 moved to a freeway bypass in 1962, the 180 co-routing followed it.

[27] In 2020, the section between Smith Road and Frankwood Avenue was upgraded to a 4-lane divided expressway which bypassed the communities of Centerville and Minkler to save eligible historic buildings on the current route.

[31] Even after funding dried up, the neighborhood declined dramatically with the ever-present knowledge that everything in its path would be demolished as soon as the money appeared;[32] low property values led to many buildings becoming slums or being condemned and razed long before the freeway came.

[34] Except where prefixed with a letter, postmiles were measured on the road as it was in 1964, based on the alignment that existed at the time, and do not necessarily reflect current mileage.