The significance of the Lewis and Clark expedition in U.S. history was its exploration and mapping of the newly acquired western territories after the Louisiana Purchase in 1803. Commissioned by President Thomas Jefferson, Meriwether Lewis and William Clark led the expedition from 1804 to 1806, traversing diverse landscapes and encountering various Native American tribes. Their gathering of scientific data, resources, and geographical information expanded understanding of the American West and fostered westward expansion. The expedition ultimately paved the way for future exploration, settlement, and federal policies that shaped the development of the United States as it pushed towards Manifest Destiny.