In one of the most famous duels in United States history, Alexander Hamilton met Aaron Burr in Weehawken on 11 July 1804. Both men were Revolutionary War veterans who held lofty positions within the new American government (Hamilton was a former secretary of the treasury and Burr then was the vice president of the United States), but their longstanding political differences and animosities would result in Hamilton's death and Burr's political ruin. Although public relations between Hamilton and Burr had appeared cordial, for many years Hamilton had worked behind the scenes to damage Burr's political career. During the course of Burr's unsuccessful campaign for the governorship of New York in 1804, published letters appeared, in which comments attributed to Hamilton portrayed Burr as a "dangerous man, who ought not to be trusted with the reins of government." The anonymous letters also alluded to Hamilton's even "more despicable opinion" of Burr. Burr was soundly defeated in the election, and believed that Hamilton was part of the reason for his loss.

Following his defeat, Burr began a war of words over the apparent affront to his honor by Hamilton. The protagonists and their seconds were unable to reach an acceptable compromise, and the place and time for the duel was set. Accounts vary as to exactly what happened-whether Hamilton fired straight up or errantly-yet the result was plain: Burr shot Hamilton in the abdomen, while he remained unscathed. Hamilton died the next day at his home in New York. Burr first fled South to avoid prosecution for murder but eventually returned to Washington to complete his term as vice president. Burr later was tried for treason for his part in what is known as the Burr Conspiracy, an attempt gain control of part of the Louisiana Purchase and secede from the United States. He was acquitted and finally returned to New York in 1812, where he succeeded in having the murder charges against him dropped and practiced law until his death in 1836.