For years, Jefferson had heard of and read accounts of the various ventures of other explorers in parts of the western frontier and consequently had a long-held interest in further exploring this largely still unknown region of the continent. Two years into his presidency, Jefferson asked Congress to fund an expedition through the Louisiana territory to the Pacific Ocean. He did not attempt to hide the Lewis (leader) and Clark expedition itself from Spanish, French, and British officials, but rather claimed different reasons for the venture.

The Corps of Discovery departed from Camp Dubois at 4 pm on May 14, 1804, The Expedition established relations with two dozen Indian nations, without whose help the expedition would have risked starvation during the harsh winters and/or become hopelessly lost in the vast ranges of the Rocky Mountains. Then they met a French-Canadian fur trapper named Toussaint Charbonneau, and his young Shoshone wife Sacagaweahere for help them. In canoes, they descended the mountains by the Clearwater River, the Snake River, and the Columbia River, past Celilo Falls, and past what is now Portland, Oregon

The Lewis and Clark Expedition gained an understanding of the geography of the Northwest and produced the first accurate maps of the area. During the journey, Lewis and Clark drew about 140 maps. Jefferson had the expedition declare "sovereignty" and demonstrate their military strength to ensure native tribes would be subordinate to the U.S., as European colonizers did elsewhere. After the expedition, the maps that were produced allowed the further discovery and settlement of this vast territory in the years that followed. 

He integrated the Whig party in 1834, becoming quickly a great figure of the Republicans. Lincoln's victory in the elections of 1860, prompted seven southern slave states to secede from the United States and form the Confederate States of America, which created, in April 12 1861, the bloodiest war in the History of the United States, the Civil War, because of his positions on important topics like slavery as said before.

He contributed a lot during the West Ward expansion because of his will to install trainrails to make it easier to conquer the west.

He was assassinated in 1865 by John Wikes Booth, a confederate sympathizer, at The Ford’s Theatre, Washington DC.