John Henry Weber was born in 1779 in Altona near Hamburg, at that time part of Denmark. By 1807 he migrated to America to Ste. Genevieve, Missouri where he became acquainted with William Ashley and Andrew Henry. In 1822 Weber enlisted in the Ashley-Henry Fur Company which departed St. Louis in the spring bound for the beaver trade of the Upper Missouri River. After reaching the mouth of the Yellowstone River, the company divided into two trapping brigades and it appears very probable that Weber commanded one of them. Certainly Weber was considered one of the most prominent members of the entire Ashley-Henry company.

For roughly the next five years, Weber's life was occupied in the Rocky Mountain fur trade, a significant portion of which was spent in Utah. During the summer of 1824, his brigade crossed South Pass and the Green River Valley and descended upon the Bear River region for the fall hunt. As winter approached, the company journeyed to "Sweet Lake" (Bear Lake), then to the Bear River's north bend and south to "Willow Valley" (Cache Valley). Weber's brigade spent the winter of 1824-25 in Cache Valley on Cub Creek, near present-day Cove, Utah. Allegedly, while in Cache Valley, discussions arose concerning the remaining course of the Bear River. A subordinate of Weber, a young Jim Bridger, was selected to settle the question by floating down the river during which voyage he came upon the Great Salt Lake. For years Bridger was credited for the first discovery of the "Great Inland Sea" until more recent evidence would indicate this honor be given to Etienne Provost.