The many streams that feed into the Weber River made the area attractive to prehistoric nomadic Native Americans, including the Shoshone and Ute tribes.

The river and canyon were named for fur trapper John Henry Weber.

In 1825, near the present-day community of Mountain Green, trappers of the British Hudson's Bay Company Snake Country Expedition, under the leadership of Peter Skene Ogden, had a confrontation with competing American trappers, under the leadership of Johnson Gardner.

Ogden kept the situation from becoming an international incident, although some of his men, including Canadian Antoine Godin, left his group to join Gardner.

[1] Emigrants traveling to California, including the Hudspeth, Bryant-Russell, and Young and Harlan parties,[2] took the first wagons through Weber Canyon in 1846.