The musical begins with the company summarizing Alexander Hamilton's early life as an orphan in the Caribbean ("Alexander Hamilton"). Hamilton was born out of wedlock in the West Indies—his father abandoned him at an early age and his mother died when Hamilton was twelve. By nineteen, Hamilton has made his way to the American colonies, a dedicated supporter of American independence.
In the summer of 1776 in New York City, Hamilton seeks out Aaron Burr. Burr advises the overenthusiastic Hamilton to "talk less; smile more". Hamilton is unable to understand why Burr would rather exercise caution than fight for his beliefs ("Aaron Burr, Sir"). Hamilton bonds with three fellow revolutionaries: 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 able and willing to fight for their submission ("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 falls instantly in love, and after being introduced by Angelica, Eliza and Hamilton soon wed ("Helpless"). Angelica is also smitten with Hamilton, but swallows her feelings for the sake of her sister's happiness ("Satisfied"). Hamilton, Laurens, Lafayette and Mulligan drunkenly celebrate the marriage when Burr arrives to offer congratulations. After Laurens teases him, Burr admits that he is having an affair with the wife of a British officer ("The Story of Tonight (Reprise)"). Hamilton urges Burr to make the relationship public. Burr, however, prefers to wait and see what life has in store for him rather than take any drastic measures ("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 ("Stay Alive"). Hamilton is offended, but Washington orders Hamilton to ignore the comments. Hamilton does not wish to do so, but cannot disobey a direct order; instead, Laurens duels Lee, with Hamilton as his second, and Burr as Lee's second. Laurens is satisfied after he injures Lee and Lee yields ("Ten Duel Commandments"). Washington is angered by 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 doesn't need fame or fortune to live a happy life by her side ("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 offers him his long-desired 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 successfully govern on their own ("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. Angelica announces that she has found a husband and will be moving to London. The newly elected President Washington enlists Hamilton for the job of Treasury Secretary, despite Eliza's protests ("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. Immediately upon returning, he briefly addresses Sally Hemings, asking her to open a letter from Washington, requesting that he become the first secretary of State under the new Constitution. Upon Jefferson's arrival in New York, James 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 debate 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 that Philip, their son, is turning nine years old. 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. She also mentions a letter recently received from Hamilton, in which he referred to her as his "dearest," and wondering if it was intentional. 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, who claims she has been deserted by her husband. 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 Schuyler's seat in the Senate. This drives a wedge between Burr and Hamilton—the latter believes that Burr holds no loyalties and will stop at nothing to gain influence ("Schuyler Defeated").
In another Cabinet meeting, Jefferson and Hamilton argue over whether the United States should assist France in its conflict with Britain. Washington ultimately agrees with Hamilton's argument for remaining neutral ("Cabinet Battle #2"). After the meeting, Burr, Jefferson, and Madison share their envy of Washington's perennial support of Hamilton's policies. They begin to seek a way to damage Hamilton's public image ("Washington on Your Side").
Washington tells Hamilton that Jefferson has resigned from his position 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 word that Washington is stepping down and will be replaced with John Adams. The king exits merrily, ready to enjoy the United States' suffering through the political turmoil caused by transitions in leadership, and Adams' inexperience ("I Know Him").
Hamilton is fired by Adams and publishes an inflammatory critique of the new president as a response ("The Adams Administration"). Jefferson, Madison and Burr believe they have found proof that Hamilton embezzled government money, effectively committing treason. When confronted, Hamilton admits to his affair with Maria Reynolds and his furtive payments to James Reynolds ("We Know"). Though the men swear to keep his secret, Burr reminds Hamilton that rumors grow, and Hamilton worries that the truth will get out. He reflects on 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. His personal reputation, however, is ruined following the Reynolds Pamphlet's publication ("The Reynolds Pamphlet"). Heartbroken by his infidelity, Eliza tearfully burns the letters Hamilton has written her over the years, 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 Philip, now grown, challenges George Eacker to a duel for insulting his father. Following Alexander's advice, Philip aims for the sky at the beginning of the duel, hoping the gesture would cause Eacker to stand down, 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 family moves uptown. Hamilton asks for Eliza's forgiveness for his mistakes, which he eventually receives ("It's Quiet Uptown").
The presidential election of 1800 results in President John Adams' defeat, with Jefferson and Burr tied to win. Hamilton is upset that Burr holds no apparent principles, and so endorses Jefferson, who wins the presidency ("The Election of 1800"). Burr, angered, challenges Hamilton to a duel via an exchange of letters ("Your Obedient Servant"). Before sunrise on the morning of the duel, Eliza, unaware of the duel, asks Hamilton to come back to bed. Hamilton tells her he has an appointment, and tells her that he loves her ("Best of Wives and Best of Women").
Burr and Hamilton travel to Weehawken, New Jersey for the duel. Hamilton aims his pistol at the sky and is struck in the chest by Burr's bullet. Hamilton soliloquizes on death, his relationships, and his legacy. He dies soon after, with his wife and Angelica at his side. Burr laments that even though he survived, he is cursed to be the villain in history, remembered 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 rival's financial plans. Eliza explains her role in preserving her husband's legacy over the next 50 years and frets that she has still not done enough. Addressing Hamilton directly, she tells him that she has established a private orphanage in his honor and she "can't wait to see [him] again" ("Who Lives, Who Dies, Who Tells Your Story").