The family and several friends had reached The Dalles, and had loaded everything and everyone onto rafts for the final leg of their journey through the Columbia river gorge to the Willamette Valley. Near The Dalles, tragedy struck the Applegate clan. "Whirlpools looking like deep basins in the river, the lapping, splashing, and rolling of waves... Presently there was a wail of anguish, a shriek, and a scene of confusion in our boat that no language can describe. The boat we were watching disappeared and we saw the man and boys struggling in the water."

Eleven year old Elisha and nine year old Warren Applegate were drowned. Lindsay and Jesse each lost a child to the river; Lindsay later wrote that, "We resolved if we remained in the country, to find a better way for others who might wish to emigrate."

They crossed the Umpqua River and made their way to present day Ashland, Oregon, and then crossed over Greensprings to the Klamath Basin. They passed Klamath Lake, crossed the Tule and Goose Lake valleys to northern California, and crossed Black Rock Desert to the Humboldt River where they picked up the California Trail from Fort Hall, Idaho. Jesse rode ahead of the main party to Ft. Hall to tell people of the new overland route and to get a wagon train together.

Thus the name of Applegate trail was born.