After crossing Mount Oread at Lawrence, the trail crossed the Kansas River by ferry or boats near Topeka, and crossed the Wakarusa and Vermillion rivers by ferries. After the Vermillion River the trail angles northwest to Nebraska paralleling the Little Blue River until reaching the south side of the Platte River.

The Oregon Trail Scenic Byway follows the main Oregon Trail from the crossing of the Snake River near Glenns Ferry to Bonneville Point, southeast of Boise.

Entering the northeastern corner of present-day Oregon, the trail crossed the Blue Mountains before reaching the lower Columbia River.

Within Nebraska, the Oregon Trail followed the Platte River and the North Platte River into Wyoming. Along this part of the journey, the Great Plains started giving way to bluffs and hills that were the precursor of the Rocky Mountains. After crossing the Rockies through South Pass, the trail followed the Snake River to the Columbia River.