In 1801, Meriwether Lewis was a Captain serving as the paymaster for the First Infantry Regiment of the United States Army. In March, he received a letter from Thomas Jefferson, the newly inaugurated President, asking Lewis to become his private secretary. Lewis, whose family was friends with the Jefferson clan, accepted at once, and thus began a close working relationship, one in which Jefferson became a father figure to Lewis and mentored his young subordinate on policy matters, including his dreams of western exploration and expansion.

By the time they began to assemble the Corps of Discovery in the summer of 1803, Thomas Jefferson and Meriwether Lewis knew more than anyone else about the Louisiana Territory, that immense wilderness the country had recently purchased from France. Although Jefferson had never ventured more than fifty miles west from Monticello, he had dreamed of the trans-Mississippi and studied the region extensively over the previous two decades, even trying unsuccessfully to send exploratory expeditions on several occasions.

The dream of finding an all water route across North America, the mythical Northwest Passage, had been imagined since the time of Christopher Columbus. Incredibly, three hundred years after the Admiral of the Ocean Seas completed his epic voyages, the vast interior of the continent was still essentially unknown to Europeans. This great uncertainty led to numerous theories about what lay beyond what men could see.