Jefferson defeated John Adams in the 1800 presidential election, marking a significant victory for the Democratic-Republican Party. The election was hard-fought and bitterly contested, and Jefferson's victory represented a shift in American politics away from Federalist control. The peaceful transfer of power was an important precedent.

In his inaugural address, Jefferson emphasized the importance of unity, limited government, and protection of individual liberties. He famously declared, 'We are all Republicans, we are all Federalists,' seeking to heal the divisions of the previous decade.

Jefferson orchestrated the Louisiana Purchase, acquiring a vast territory from France that doubled the size of the United States. This was a momentous achievement that secured American control of the Mississippi River and opened up vast new lands for westward expansion. The purchase required a loose interpretation of the Constitution, which conflicted with Jefferson's previous stance.

Jefferson commissioned the Lewis and Clark Expedition to explore the newly acquired Louisiana Territory. The expedition provided valuable information about the geography, natural resources, and indigenous peoples of the region, furthering American knowledge and claims to the territory.

Jefferson authorized military action against the Barbary pirates in North Africa, who were attacking American merchant ships. This conflict demonstrated American resolve to protect its maritime interests and established the United States as a naval power.