The main course of the river is short, formed in the Willamette Valley by the confluence of the North and South Santiam rivers on the border between Linn and Marion counties approximately 8 mi (13 km) northeast of Albany. It flows generally WNW in a slow meandering course to join the Willamette from the east approximately 8 mi (13 km) north of Albany.
Both the North and South Santiam rise in high Cascades in eastern Linn County. The Middle Santiam River joins the South Santiam where the South Santiam is impounded to form Foster Lake. The North Santiam is impounded to form the 400-ft (120 m) deep Detroit Lake in the Cascades. The Santiam is a major source of water supply for Salem.
Santiam City was a small community built along the river's banks during Oregon's settlement in the 1850s, but was destroyed by the Great Willamette Flood of 1861 which crested on December 2, 1861.123
