Born at Vincennes, Indiana, William Henry Vanderburgh was born to Judge Henry Vanderburgh and Frances Cornoyer Vanderburgh on December 6, 1800, the fifth of ten children. He grew up to attend West Point for four years but did not graduate. He then went to work for the Missouri Fur Company near Council Bluffs, Iowa, under Manual Lisa and Joshua Pilcher.
A short-lived Fort Vanderburgh, North Dakota, was named for him in 1821. He took part in the Arikara War in 1823. In 1826, he and several others formed a fur trading company to succeed the Missouri Fur Company, and the following year was wintering on the Green River in Wyoming.
In the winter of 1828, he was trading with the Ponca Indians in Nebraska. Later, he worked under Kenneth McKenzie of the American Fur Company at Fort Union, North Dakota, and led 50 men to the Green River in the summer of 1830. He continued to trade through the mountains and took part in the Battle of Pierre’s Hole, Idaho, against Gros Ventre warriors on July 18, 1832.
Later that year, he and another trapper named Alexis Pilou, while in the vicinity of Alder Gulch, Montana, were killed in an Indian ambush on October 14, 1832. His body was never recovered.