Arising in the Cascade Range near Mount Hood, it flows northeast then west to its confluence with the Columbia near The Dalles.

It was named "fifteenmile" because in pioneer days the main road crossed the creek about fifteen miles (24 km) from The Dalles.

[6] Fifteenmile Creek's headwaters are near Lookout Mountain in the Cascade Range, east of Mount Hood.

[1][5] Several species of anadromous fish inhabit streams in the watershed, including steelhead, Pacific lamprey, chinook and coho salmon.

[8] Populations have declined in recent years, due to a combination of overfishing, an increase of hydroelectric dams, and general worsening of habitat conditions.