The second of three children of Lucy and John Lewis of Virginia, Lewis joined the US Army in 1794 and rose to the rank of Captain in 1800. In 1801 Captain Lewis became private secretary to U.S. President Thomas Jefferson. Under Jefferson’s direction, Lewis planned an exploration of a route west to the Pacific coast of North America. He invited William Clark to join the expedition, and the two men privately agreed to lead it jointly. In addition to command, Lewis served as the party’s naturalist. On the expedition he collected plant, animal, and mineral specimens.

In May of 1804 the expedition started up the Missouri River from a camp near St. Louis. By late fall, the explorers reached what is now North Dakota and spent the winter there. The following spring they continued along the Missouri and in late summer crossed the Rocky Mountains. They obtained horses, supplies, and valuable information from the Native American tribes they met on their journey. Following the Clearwater, Snake, and Columbia Rivers they made their way to the Pacific coast, which they reached in November of 1805. The party spent the winter on the coast of what is now Oregon and began the trip home in March of 1806. The explorers returned along nearly the same route by which they had come, reaching St. Louis in September of 1806 after traveling a total of 8,000 miles (12,800 kilometers).

In 1809 Lewis died under ambiguous circumstances. It is speculated that personal and professional problems may have driven him to suicide, but some people believe he was murdered.