Hamilton, one of the Founding Fathers of the United States, was an instrumental promoter of the U.S. Constitution, founder of the nation's financial system, and its first Secretary of the Treasury.

He later cited his change in focus, "as a way to broaden my scope, and to stay fresh" after being inundated with requests for further biographies about Gilded Age industrialists such as Andrew Carnegie and Cornelius Vanderbilt.

He held the dueling pistols used in the famous Burr–Hamilton duel, visited the jail cell on Saint Croix where Hamilton's mother was imprisoned, went to the island of Bequia in Saint Vincent and the Grenadines to which Hamilton's father disappeared after abandoning his illegitimate son, and had a lock of Alexander's hair genetically tested for his racial makeup.

"[12] Maslin praised Chernow's biographical ability to "add a third dimension to conventional views of Hamilton while reaching beyond the limits of a personal portrait".

[6] However, Benjamin Schwarz, writing for The Atlantic, criticized the book, blaming Chernow's unfamiliarity with revolutionary American politics.

While he praised Chernow's earlier biographies about Morgan and Rockefeller, his review of Hamilton stated, "he's just as obviously not at home in the eighteenth century; his grasp of its religion, attitudes, and intellectual history is unsure, and he lacks command of the ideological, political, sectional, and social differences that divided the early republic.

"[13] Justin Martin, writing for the San Francisco Chronicle additionally thought the book "dry and speculative," as well as slow in pace; "one can only assume that Chernow, despite his abundant talent, is in the grip of a silly literary convention, namely, that bios of major figures must be very, very long.

[15] Miranda told Chernow that he saw "hip-hop songs rising off the page" while reading the biography and wanted his help as a historical consultant for the musical.