Nebraska was part of the Louisiana Purchase, after which President Thomas Jefferson requested that a geographic expedition of the area be undertaken. The Lewis and Clark Expedition crossed the eastern edge of what now is Nebraska. Missionaries, traders, trappers, and travelers moved across Nebraska between 1800 and 1840.

The Oregon Trail followed the Little Blue and Platte Rivers through Nebraska, and was used by thousands of wagon trains between 1830 and 1870. The Mormon Trail to Utah and The Denver Trail to Colorado also crossed Nebraska. Nebraska was part of the Indiana Territory from late 1804 until July 4, 1805. From then until December 7,1812, it was part of the Louisiana Territory. It then became part of Missouri Territory until 1821, when Missouri became a state and Nebraska was part of the unorganized region known as "Indian country." The first federal bill organizing the territory was passed in 1854: the Kansas -Nebraska Act. The first session of the territorial legislature met January 16, 1855. Statehood finally was achieved in 1867.