Thomas Jefferson dies at Monticello at the age of 83, on the 50th anniversary of the adoption of the Declaration of Independence. His death coincides with that of John Adams, marking a symbolic end to the era of the Founding Fathers.

Thomas Jefferson, prompted by tensions with both Britain and France, leads the enactment of the Embargo Act of 1807, a controversial policy aimed at restricting American trade with foreign powers. This act ultimately triggers economic turmoil in the United States and faces strong criticism, leading to its eventual abandonment a year later.

Congress passes the Act Prohibiting Importation of Slaves, which Jefferson signs into law. This act prohibits the international slave trade, although it does not address the domestic issue of slavery.

Aaron Burr is captured in Louisiana and sent to Virginia to be tried for treason. Jefferson orders Burr's arrest after discovering Burr's plot to seize territory in the West.

Congress approves the Non-Importation Acts, which are aimed at boycotting British goods in response to the Royal Navy's practice of stopping American merchant ships and impressing sailors into service. However, these acts are not actively enforced, leading to continued tensions between the United States and Britain.

President Thomas Jefferson, in his annual message to Congress, voices strong opposition to Spain over alleged border depredations in Florida. Shortly thereafter, he makes a secret request for a two-million-dollar expenditure to facilitate the purchase of Florida from Spain. This action underscores Jefferson's intent to annex West Florida and reflects his administration's pursuit of territorial expansion. However, the effort ultimately proves unsuccessful, damaging Jefferson's standing among his supporters.

Aaron Burr fatally wounds Alexander Hamilton in a duel. This event has significant political ramifications and further strains the already tense relationship between Jefferson and his vice president, Burr.

The U.S. Senate ratifies the Louisiana Purchase treaty, doubling the size of the United States. This is a significant achievement of Jefferson's presidency, promoting western expansion and securing control of the Mississippi River.

President Thomas Jefferson signs the Military Peace Establishment Act, establishing the United States Military Academy at West Point.

Thomas Jefferson is inaugurated as the third President of the United States, marking a peaceful transition of power from the Federalist to the Democratic-Republican Party.

Thomas Jefferson writes a letter to Benjamin Rush, a quote from which he engraved around the Jefferson Memorial: "I have sworn upon the altar of God eternal hostility against every form of tyranny over the mind of man".

Thomas Jefferson gave a lecture, later published as a paper in 1799, which reported on the skeletal remains of an extinct large sloth, which he named Megalonyx, unearthed by saltpeter workers from a cave in what is now Monroe County, West Virginia. Jefferson is considered to be a pioneer of scientific paleontology research in North America.

Thomas Jefferson becomes the third president of the American Philosophical Society (APS). In accepting, Jefferson stated: "I feel no qualification for this distinguished post but a sincere zeal for all the objects of our institution and an ardent desire to see knowledge so disseminated through the mass of mankind that it may at length reach even the extremes of society, beggars and kings."

Thomas Jefferson ends writing his Autobiography of Thomas Jefferson: 1743–1790.

Thomas Jefferson assumes office as the first United States Secretary of State under President George Washington. He is responsible for foreign affairs and plays a key role in shaping early American foreign policy. He serves until December 31, 1793.

Thomas Jefferson is appointed by the Congress of the Confederation to join Benjamin Franklin and John Adams in Paris as Minister Plenipotentiary for Negotiating Treaties of Amity and Commerce with Great Britain and other countries. This appointment signifies his role in shaping U.S. foreign policy during this period.

Martha Wayles Skelton Jefferson, Thomas Jefferson's wife, dies after ten years of marriage. Her death profoundly affects Jefferson, leading him to promise never to remarry.

The Continental Congress formally adopts the Declaration of Independence, primarily authored by Thomas Jefferson. This marks a pivotal moment in American history, declaring the colonies' independence from Great Britain. Jefferson's preamble is considered an enduring statement on individual and human rights.

Thomas Jefferson is named Colonel and commander of the Albemarle County Militia at the start of the American Revolutionary War. This marks his involvement in the military aspect of the revolution.

Thomas Jefferson marries Martha Wayles Skelton, a 23-year-old widow and his third cousin. Their marriage is considered a happy period in Jefferson's life, during which they have six children.

Thomas Jefferson's sister Martha marries Dabney Carr, Jefferson's close friend and college companion. This is a significant event in Jefferson's personal life.