Meriwether Lewis was born on 18 August 1774 near Ivy, seven miles west of Charlottesville, Virginia Colony, on the eve of the American Revolution. His father died when Meriwether was five years old. His mother remarried and the family moved to Georgia. There he learned frontier skills. At the age of thirteen, Lewis returned to Albemarle County, Virginia, to live with relatives in Cloverfield. In 1788-1790, Lewis was able to gain an education from a series of tutors: Parson Matthew Maury, Dr. Charles Everitt, and Reverend Jaines Waddell. In 1792, he moved his twice widowed mother back to Virginia. Here he set up and took on the responsibility of managing the family household and property at Locust Hill. This ended Lewis' formal academic education. For his day, Lewis was well educated. Lewis was tall and thin and had light-colored hair. He gained practical experience and skills while running the family plantation. At the age of 20, he enlisted in the Virginia Volunteer Corps. In the fall of 1795, Ensign Lewis was reassigned to the Chosen Rifle Company under the command of William Clark. By 1800, Lewis attained the rank of Captain of the First Infantry of the U.S. Army.

In 1801, Lewis accepted a position as secretary to the President, Thomas Jefferson, and lived in the presidential residence in the City of Washington. Thirty-one years his senior, Jefferson became Lewis' mentor. By the fall of 1802, Lewis was preparing for the exploration of western North America by acquiring an education in geography, botany, mineralogy and astronomy. He studied with Andrew Ellicott and Robert Patterson to learn celestial navigation, with Dr. Benjamin Rush to learn field medical treatments and to make a field medicine chest, with Dr. Benjamin Smith Barton to learn botany, natural history and how to prepare specimens, and finally with Dr. Caspar Wistar to learn about paleontology. Years later in a biography of Lewis, Jefferson reaffirmed his confidence in Lewis as a leader of the exploration expedition:

"Of courage undaunted, possessing a firmness & perseverance of purpose which nothingbut impossibilities could divert from it's direction, careful as a father of those committed to his charge, yet steady in the maintenance of order & discipline, intimate with the Indian character, customs & principles, habituated to the hunting life, guarded by exact observation of the vegetables & animals of his own country, against losing time in the description of objects already possessed, honest, disinterested, liberal, of sound understanding and a fidelity to truth so scrupulous that whatever he should report would be as certain as if seen by ourselves, with all these qualifications as if selected and implemented by nature in one body, for this express purpose, 1 could have no hesitation in confiding the enterprise to him."

Lewis was successful in leading the Corps of Discovery. He shared the information about the west with President Jefferson and the science community in Philadelphia. In 1807, he was appointed Governor of the Louisiana Territory and stationed in St. Louis. Lewis had made many of the arrangements needed to illustrate and publish his journals of the expedition, but he was never able to work on or provide the manuscript. By 1809, he faced political difficulties and financial problems, as well as family and personal disappointments.

William Clark was born in Caroline County on 1 August 1770 near Charlottesville, Virginia Colony. He was the ninth child in a large and well known family. George Rogers Clark, who secured the Ohio Territory for the United States during the Revolutionary War, was his oldest brother. The family moved to Kentucky when William was fourteen years old. The black slave, York, was his companion since childhood. William was tall and had red hair. Clark joined the army in 1792 and served in the Ohio Territory. He attained the rank of Captain three years later. Ensign Meriwether Lewis served under him in the Chosen Rifle Company. Clark resigned his commission in 1796 to take care of the family business in Kentucky and Indiana. However, he still kept in touch with Lewis.

President Jefferson approved Lewis' choice of Clark as the co-leader of the planned expedition to the Pacific. The U.S. Army would not reinstate Clark with his former rank of Captain. He received the rank of 2nd Lieutenant of the Corps of Artillerists. Lewis always called Clark by the title of "captain" and never told the members of the Corps of Discovery otherwise. (Clark's slave, York, accompanied him on the expedition.)

While on the expedition, Clark kept a daily journal and produced all the maps of the expedition's route. The compilation map was the most complete of the land west of the Mississippi River for that time period. Much of the success of the expedition can be attributed to how well Lewis and Clark worked together to lead the Corps of Discovery. Their skills and personalities were individual yet complimentary.

Shortly after the expedition, Clark married Julia Hancock of Fincastle, Virginia, whom he had courted before the trip began. They had four sons and a daughter. After Julia's death in 1820, Clark married a widow, Harriet Kennerly, and they had two sons. Julia and Harriet were cousins.

Jefferson appointed Clark to be Superintendent of Indian Affairs for the Louisiana Territory with the rank of Brigadier General of the Militia. He was stationed in St. Louis. In 1808, Clark became one of the partners in the St. Louis Missouri River Fur Company. Clark was appointed Governor of the Missouri Territory in 1810.

After the tragic and untimely death of Lewis, Clark persuaded Nicholas Biddle to prepare a manuscript for publication of both Lewis' and Clark's journals from the expedition. With the help from Clark and George Shannon, one of the enlisted men on the expedition, the work took Biddle two years to complete, 1810-1812. Royalties from the sale of the published journals were to go to Clark, but he never received a penny. He tried to keep track of all the members of the Corps of Discovery, and twenty years later, his list contained thirty-four names, eighteen of whom were known dead by 1825.

On 1 September 1838, William Clark died. He was buried in Bellefontaine Cemetery near St. Louis, Missouri. There is a large and elaborate memorial at his grave site.