[2] Burr portrays the eponymous anti-hero as a fascinating and honorable gentleman, and portrays his contemporary opponents as mortal men; thus, George Washington is an incompetent military officer, a general who lost most of his battles; Thomas Jefferson is a fey, especially dark and pedantic hypocrite who schemed and bribed witnesses in support of a false charge of treason against Burr, to whom he almost lost in the 1800 United States presidential election; and Alexander Hamilton is a bastard-born, over-ambitious opportunist whose rise was by General Washington's hand, until being fatally wounded in the 1804 Burr–Hamilton duel.

To break the tied electoral vote, the House of Representatives—dominated by Alexander Hamilton—voted thirty-six times, until they elected Jefferson, and by procedural default named Burr as the vice president.

The other gives us, by means of Burr's recollections as read and recorded by Schuyler, his experience of late eighteenth century British colonial life and the independence struggle or "Revolution" (in the section called 1833); and most substantially, his experience of life in post-Independence New York and his participation in the political development of the American Republic (through the main section of the novel, 1834), thus: Vidal notes in the novel's afterword that each character named therein "actually existed,"[9] with the exception of its narrator, Charlie Schuyler, and William de la Touche Clancey, a thinly veiled satire of longtime Vidal critic William F. Buckley Jr.[10] The sections of the novel that deal with the narrator's activity in the 1830s (as opposed to Burr's reminiscences of his adventures in the American Revolution through his trial for treason) focus on the political life of New York City during the end of the administration of President Andrew Jackson.

In his review for The New York Times, Christopher Lehmann-Haupt lauded the novel as a "a tour de force of historical imagination", praising the plot as a "clever piece of machinery" whilst noting the "rather far-fetched and clumsy denouement".

[11][12] Kirkus Reviews praised the novel as "a clever book", noting the timeliness of its iconoclastic treatment of certain Founding Fathers "considering our mood of national discontent" amid the then-ongoing Watergate scandal.