The musical begins with the company summarizing Alexander Hamilton's early life as an orphan in the Caribbean ("Alexander Hamilton").
In the summer of 1776 in New York City, Hamilton seeks out Aaron Burr. Burr advises him to "talk less; smile more." Hamilton rebuffs Burr's philosophy ("Aaron Burr, Sir") and instead joins three revolutionaries he meets: abolitionist John Laurens, the flamboyant Frenchman Marquis de Lafayette, and the tailor's apprentice Hercules Mulligan. Hamilton dazzles them with his rhetorical skills ("My Shot") and they dream of laying down their lives for their cause ("The Story of Tonight"). Meanwhile, the wealthy Schuyler sisters—Angelica, Eliza, and Peggy—wander the streets of New York, excited by the spirit of revolution in the air ("The Schuyler Sisters").
Samuel Seabury, a vocal Loyalist, preaches against the American Revolution, and Hamilton refutes and ridicules his statements ("Farmer Refuted"). A message arrives from King George III, reminding the colonists that he is willing and able to fight for their love ("You'll Be Back").
The revolution is underway, and Hamilton, Burr, and their friends join the Continental Army. As the army retreats from New York City, General George Washington realizes he needs help to win the war. Though Hamilton desires a command and to fight on the front lines, he recognizes the opportunity Washington offers him, and accepts a position as his aide-de-camp ("Right Hand Man").
In the winter of 1780, the men attend a ball given by Philip Schuyler, and Hamilton sets his sights on the man's daughters ("A Winter's Ball"). Eliza is instantly smitten, and after being introduced by Angelica, Eliza and Hamilton soon wed ("Helpless"). Meanwhile, Angelica is also intellectually and physically attracted to Hamilton, but swallows her feelings for the sake of her sister's happiness ("Satisfied"). Burr arrives to offer congratulations, and privately admits to Hamilton that he is having an affair with the wife of a British officer. Hamilton advises him to take action ("The Story of Tonight (Reprise)"). Burr, however, prefers to wait and see what life has in store for him ("Wait For It").
As the revolution continues, Hamilton repeatedly petitions Washington to give him command, but Washington refuses, instead promoting Charles Lee. This decision proves disastrous at the Battle of Monmouth, where Lee orders a retreat against Washington's orders, which prompts the commander to remove him from command in favor of Lafayette. Disgruntled, Lee spreads slanderous and vindictive rumors about Washington. Hamilton is offended, but Washington orders Hamilton to ignore the comments. Laurens, now also an aide to Washington, volunteers to duel Lee so that Hamilton may avoid disobeying Washington's orders ("Stay Alive"). Laurens wins the duel by injuring Lee ("Ten Duel Commandments"). Washington is enraged at the duel, and orders Hamilton to return home to his wife ("Meet Me Inside"). When Hamilton returns home, Eliza tells him she is pregnant. She reassures a hesitant Hamilton that he is enough for her ("That Would Be Enough").
Lafayette takes a larger leadership role in the revolution, persuading France to join the American cause, and the balance shifts in favor of the Continental Army. Washington and Lafayette realize they can win the war by cutting off the British navy at Yorktown, but they will need Hamilton to do so, and the general reluctantly gives him his long-awaited command ("Guns and Ships"). On the eve of battle, Washington recalls his disastrous first command, and advises Hamilton that no man can control how he is remembered ("History Has Its Eyes on You"). After several days of fighting, the Continental Army is victorious. The British surrender in the last major battle of the war ("Yorktown (The World Turned Upside Down)"). His forces defeated, King George asks the rebels how they expect to govern on their own without their people hating them ("What Comes Next?").
Soon after the revolution, Hamilton's son Philip is born, while Burr has a daughter, Theodosia ("Dear Theodosia"). Hamilton receives word that Laurens has been killed in a seemingly pointless battle and throws himself into his work. ("Tomorrow There'll Be More Of Us"). Hamilton and Burr both return to New York to finish their studies and pursue careers as lawyers. Burr is in awe of Hamilton's unyielding work ethic and becomes increasingly irritated by his success. Hamilton is chosen as a delegate to the Constitutional Convention in the summer of 1787. Hamilton enlists James Madison and John Jay to write The Federalist Papers after Burr refuses. The newly elected President Washington enlists Hamilton for the job of Treasury Secretary, despite a helpless Eliza's pleas ("Non-Stop").
In 1789, Thomas Jefferson returns to the U.S. from France, where he spent most of the Articles of Confederation era as an ambassador. Washington has asked him to be Secretary of State under the new Constitution, and Madison asks for Jefferson's help to stop Hamilton's financial plan, which Madison believes gives the government too much control ("What'd I Miss?"). Jefferson and Hamilton then engage in debate over the merits of Hamilton's financial plan during a Cabinet meeting. Washington pulls Hamilton aside, and tells him to figure out a compromise to win over Congress ("Cabinet Battle #1").
While Hamilton is working at home, Eliza reminds him of Philip's ninth birthday. Philip presents Hamilton with a short rap he composed, amazing his father. Angelica advises Hamilton to convince Jefferson of his plan so Congress will accept it. Later, Eliza and Angelica try to persuade Hamilton to accompany them on vacation for the summer, but Hamilton refuses, saying that he has to work on his plan for Congress, staying in New York while the family goes upstate ("Take a Break").
While alone, Hamilton is visited by Maria Reynolds, whose husband is mistreating her. When Hamilton offers to help her, they begin an affair. Maria's husband James Reynolds blackmails Hamilton, who is furious with Maria but pays Reynolds and continues the affair ("Say No To This").
Hamilton discusses his plan with Jefferson and Madison over a private dinner, which results in the Compromise of 1790, giving support to Hamilton's financial plan in exchange for moving the United States capital from New York to Washington, D.C., a site much closer to Jefferson's home in Virginia. Burr is envious of Hamilton's sway in the government and wishes he had similar power ("The Room Where It Happens"). Burr switches political parties and defeats Eliza's father, Philip Schuyler, in a race for his seat in the Senate, driving a wedge between Burr and Hamilton ("Schuyler Defeated").
In another cabinet meeting, Jefferson and Hamilton argue over whether the United States should assist France in their revolution. Washington ultimately agrees with Hamilton's argument for remaining neutral ("Cabinet Battle #2"). After the meeting, Burr, Jefferson, and Madison bemoan how nice it must be for Hamilton to always have Washington's support, and they seek a way to damage Hamilton's image ("Washington on Your Side").
Washington tells Hamilton that Jefferson has resigned from his position in government in order to run for president, and that Washington himself is stepping down. Hamilton is shocked, but Washington convinces him that it is the right thing to do, and they write a farewell address ("One Last Time"). In England, King George III receives news about Washington's step down from leadership and the election of John Adams. The king exits merrily, ready for the United States to fall under Adams' leadership ("I Know Him").
Adams and Hamilton have a huge altercation and effectively destroy the Federalist Party ("The Adams Administration"). Jefferson, Madison and Burr think they have discovered a scandal capable of destroying Hamilton accusing him of embezzling government money and committing treason. In reality, however, they found the transactions from his affair with Maria Reynolds. Hamilton, knowing that the truth is the only way out, tells them about his affair and begs them not to tell anyone ("We Know"). Still worried that they will tell, Hamilton thinks about how writing openly and honestly has saved him in the past ("Hurricane"), and publishes a public admission about the affair, hoping to snuff out rumors of embezzlement and save his political legacy ("The Reynolds Pamphlet"). His personal reputation, however, is ruined. In despondence, Eliza tearfully burns their correspondence, destroying Hamilton's chance at being redeemed by "future historians" and keeping the world from knowing how she reacted by "erasing herself from the narrative" ("Burn").
Years pass, and Hamilton's son Philip challenges a man named George Eacker to a duel for his slander of Hamilton's reputation. Philip aims for the sky from the beginning of the duel, but at the count of seven, Eacker shoots him ("Blow Us All Away"). Philip is taken to a doctor, who is unable to save him. Hamilton and Eliza separately arrive not long before Philip dies ("Stay Alive (Reprise)"). In the aftermath of Philip's death, the Hamiltons move uptown. Hamilton asks for Eliza's forgiveness, which he eventually receives ("It's Quiet Uptown").
The presidential election of 1800 results in President John Adams being defeated, with Jefferson and Burr deadlocked in a tie. Hamilton is upset that Burr has once again changed his ideals for personal gain, and instead throws his support behind Jefferson, who ends up winning the delegates by a landslide ("The Election of 1800"). Burr, enraged, exchanges letters with Hamilton and challenges him to a duel ("Your Obedient Servant"). Before sunrise on the morning of the duel, Eliza asks Hamilton to come back to bed, but he says he has to leave before lovingly complimenting her ("Best of Wives and Best of Women").
Burr and Hamilton travel to Weehawken, New Jersey for the duel, near the site where Philip was shot. As a gunshot sounds, Hamilton soliloquizes on death, his relationships, and his legacy. He aims his pistol at the sky and is struck by Burr's shot, dying soon after. Burr laments that even though he survived, he's cursed to be the villain in history, remembered only as the man who killed Alexander Hamilton ("The World Was Wide Enough").
The company congregates to close the story. Washington enters and reminds the audience that they have no control over how they will be remembered. Jefferson and Madison collectively admit the genius of their political rival's work. Eliza explains how she fought to save her husband's legacy over the next 50 years and frets that she has not done enough, and she then asks herself who will tell her story once she is gone. As she dies, she finds Hamilton once more in the afterlife and he shows her all those who will care for and protect her legacy as she did for him. She looks out to the audience and gasps as she realizes that her story has indeed been told ("Who Lives, Who Dies, Who Tells Your Story").