At about 22 miles (35 km) from the mouth, the river turns away from Highway 26 and flows generally north-northwest for the rest of its course.

About 1 mile (1.6 km) further downstream, Bear Creek enters from the left, and the river flows around Indian John Island.

Shortly thereafter, the river passes under Interstate 84 and flows by Portland-Troutdale Airport, which is on the left about 2 miles (3.2 km) from the mouth.

The confluence is about 14 miles (23 km) east of Portland, near the lower end of the Columbia River Gorge.

[6] Archeological evidence suggests that Native Americans lived along the lower Columbia River as early as 10,000 years ago.

The area near what later became The Dalles, on the Columbia east of the mouth of the Sandy River, eventually became an important trading center.

The Indians established villages on floodplains and traveled seasonally to gather huckleberries and other food on upland meadows, to fish for salmon, and to hunt elk and deer.

More recently, within the past few thousand years, Indians created trails across the Cascade Range around Mount Hood.

The trail network linked the trading center at Wascopam, near The Dalles, to settlements in the Willamette Valley.

[12] In 1805 and again in 1806, members of the Lewis and Clark Expedition explored the lower stretches of the Sandy River as they traveled down the Columbia to the Pacific Ocean.

[13] On November 3, 1805, William Clark wrote: "I arrived at the entrance of a river which appeared to Scatter over a Sand bar, the bottom of which I could See quite across and did not appear to be 4 Inches deep in any part; I attempted to wade this Stream and to my astonishment found the bottom a quick Sand, and impassable ...".

[12] One of the first documented visits by European-Americans to the upper Sandy River basin occurred in 1838, when Daniel Lee, the nephew of missionary Jason Lee, used the Indian trail over Lolo Pass to drive cattle from a Methodist mission in the Willamette Valley to a mission in Wascopam.

Portland General Electric, the dams' owner, donated 1,500 acres (6.1 km2) of land in the vicinity to a nature reserve.

[16] With the Marmot Dam removal and other habitat restoration in the Sandy River Basin Salmon, Steelhead, and Pacific lamprey are making a comeback.