It drains an area of the Cascade Range into the Willamette Valley east of Corvallis.

[4] It rises in the Cascades in southeastern Linn County in the Willamette National Forest at 44°22′27″N 122°13′05″W / 44.374291°N 122.218128°W / 44.374291; -122.218128 (South Santiam River source).

[1] From this source, the confluence of Sevenmile and Latiwi creeks, it flows briefly north, then generally west through the Western Cascades and Cascadia.

Downstream from the reservoir it flows west past Sweet Home, where it turns northwest, passing through the foothills into the Willamette Valley near Lebanon.

Then come Ralston, Gadney, Wiley, Ames, Roaring, McDowell, Hamilton, and Onehorse creeks followed by Spring Branch.