The first of many explorers of the uncharted regions of the newly acquired Louisiana Territory were Meriwether Lewis and William Clark. They were followed by other government sponsored expeditions led by pathfinders Pike, Long, and Frémont, among others. These men established important new routes for many who followed.

President Thomas Jefferson commissioned army officers Meriwether Lewis and William Clark to explore the Louisiana Territory, investigate potential resources, establish trade with the Indians and most importantly discover a passage to the Pacific Ocean through the Northwest. In 1803 President Jefferson presented Captain Lewis with a list of written instructions, saying that, "The object of your mission is to explore the Missouri River, and such principal streams of it which may offer the most direct and practicable water communication across the continent for the purposes of commerce..."