It flows for 167 miles (269 km)[6] southwestwards, primarily through the Palouse region of southeastern Washington.

Its canyon was carved out by a fork in the catastrophic Missoula Floods of the previous ice age, which spilled over the northern Columbia Plateau and flowed into the Snake River, eroding the river's present course in a few thousand years.

The river originates in Idaho in northeastern Latah County, in the Hoodoo Mountains in the St. Joe National Forest.

(Paradise Creek parallels the South Fork, running through Moscow to Pullman, accompanied by the Bill Chipman Palouse Trail and State Route 270.)

[7][10] The area is characterized by interconnected and hanging flood-created coulees, cataracts, plunge pools, kolk created potholes, rock benches, buttes and pinnacles typical of scablands.