Hamilton narrates Alexander Hamilton's life in two acts, and details among other things his involvement in the American Revolutionary War as an aide-de-camp to George Washington, his marriage to Elizabeth Schuyler Hamilton, his career as a lawyer and secretary of the treasury, and his interactions with Aaron Burr which culminates in their duel at the end of Hamilton's life.
The orphan Alexander Hamilton experiences a hard early life, and through his smarts and the charitability of the townsfolks leaves his home, the island of Nevis ("Alexander Hamilton"). As a student at King's College in New York in 1776, Hamilton meets Aaron Burr, John Laurens, the Marquis de Lafayette, and Hercules Mulligan ("Aaron Burr, Sir"), and impresses them with his rhetorical skills ("My Shot"). The latter three and Hamilton affirm their revolutionary goals to each other, while Burr remains apprehensive ("The Story of Tonight"). Later, the daughters of the wealthy Philip Schuyler—Peggy, Angelica, and Eliza—go into town and share their opinion on the upcoming revolution ("The Schuyler Sisters"). Loyalist bishop Samuel Seabury argues against the revolution ("Farmer Refuted") and King George III insists on his authority ("You'll Be Back"). During the New York and New Jersey campaign, Hamilton accepts a position as George Washington's aide-de-camp despite longing for field command ("Right Hand Man").
At a ball hosted by Philip Schuyler ("A Winter's Ball"), Eliza falls helplessly in love with Hamilton, who reciprocates her feelings to the point of marriage ("Helpless"), as Angelica suppresses her own feelings for the sake of their happiness ("Satisfied"). After the wedding, Burr and Hamilton congratulate each other's successes ("The Story of Tonight (Reprise)") while Burr reflects on Hamilton's swift rise while considering his own more cautious career as well as his affair with Theodosia, the wife of a British officer ("Wait For It").
As conditions worsen for the Continental Army ("Stay Alive"), Hamilton aids Laurens in a duel against Major General Charles Lee ("Ten Duel Commandments"), after which Washington temporarily suspends him from the army ("Meet Me Inside"). Back home, Eliza reveals that she is pregnant with their first child, Philip, and asks Hamilton to slow down to take in what has happened in their lives ("That Would Be Enough"). After Lafayette persuades France to get involved on the colonists' side, he urges Washington to call Hamilton back to help plan the final Battle of Yorktown. Washington agrees ("Guns and Ships"), but explains to Hamilton, who is convinced that he should die a martyr and a hero in war, that he should be wary of what he does next because whatever he does will be known for all time ("History Has Its Eyes on You"). At the Battle of Yorktown, Hamilton meets up with Lafayette to take down the British, revealing that Mulligan was recruited as a spy, helping them figure out how to trap the British and win the war ("Yorktown (The World Turned Upside Down)").
Soon after the victory of Yorktown, King George asks the newborn America how it will succeed on its own ("What Comes Next?"). Hamilton's son Philip is born, while Burr has a daughter, Theodosia, and the two tell their children how they will do anything to protect them ("Dear Theodosia"). Hamilton receives word that his long-time friend John Laurens has been killed in a seemingly pointless battle after the war was won and throws himself into his work ("The Laurens Interlude/Tomorrow There'll Be More Of Us"). He co-authors The Federalist Papers and is selected as Secretary of the Treasury by newly elected President Washington, amidst Eliza begging Hamilton to stay and Angelica moving to London with her new husband ("Non-Stop").
Act II begins when Thomas Jefferson returns to America from being the U.S. ambassador to France, taking up his newfound position as Secretary of State ("What'd I Miss"). In 1789, Jefferson and Madison debate Hamilton's financial proposals at a Cabinet meeting. Washington tells Hamilton to figure out a compromise to win over Congress ("Cabinet Battle #1"). Eliza and her family—along with Angelica, back from London—travel upstate during the summer, while Hamilton stays home to work on the compromise ("Take a Break"). Hamilton begins an affair with Maria Reynolds, making him vulnerable to her husband's blackmail ("Say No To This"). Hamilton, Jefferson, and James Madison create the Compromise of 1790 over a private dinner, exchanging Hamilton's financial plan for placing the country's permanent capital on the Potomac River. Burr is envious of Hamilton's sway in the government and wishes that he had similar power ("The Room Where It Happens"). Burr switches political parties and defeats Philip Schuyler in a race for the Senate, now making Hamilton a rival ("Schuyler Defeated").
In another Cabinet meeting, Jefferson and Hamilton argue over whether the United States should assist France in its conflict with Britain. President Washington ultimately agrees with Hamilton's argument for remaining neutral ("Cabinet Battle #2"). In the wake of this, Jefferson, Madison, and Burr decide to join forces to find a way to discredit Hamilton ("Washington on Your Side"). Washington retires from the presidency after his second term, and Hamilton assists in writing a farewell address ("One Last Time"). A flabbergasted King George receives word that George Washington has stepped down, and will be replaced by Paris signatory John Adams ("I Know Him"). Adams becomes the second President and fires Hamilton, who, in response, publishes an inflammatory critique of the new president ("The Adams Administration").
Jefferson, Madison, and Burr confront Hamilton about James Reynolds's blackmail, accusing him of "[embezzlement of] government funds" ("We Know"). Desperate to salvage his political career by proving that he was merely lustful and not corrupt, Hamilton reminisces over his life and how writing has changed his life ("Hurricane"), before prophylactically publicizing his affair in the Reynolds Pamphlet, which wrecks his own reputation ("The Reynolds Pamphlet"). It also damages his relationship with Eliza, who, in a heartbroken retaliation, burns all the letters Hamilton wrote her, trying to erase herself from history ("Burn"). After graduating from college, Philip attempts to defend his father's honor in a duel with George Eacker ("Blow Us All Away") but is fatally shot ("Stay Alive (Reprise)"), eventually leading to reconciliation between Alexander and Eliza ("It's Quiet Uptown").
Hamilton's endorsement of Jefferson in the 1800 United States presidential election ("The Election of 1800") results in further animosity between Hamilton and Burr, who challenges Hamilton to a duel via an exchange of letters ("Your Obedient Servant"). Hamilton writes his last letter in a rush while Eliza tells him to go back to bed ("Best of Wives and Best of Women"). Burr reflects on the moments leading up to the duel, while Hamilton reflects on his legacy, before throwing away his shot. Burr fatally shoots Hamilton, and laments that though he survived, he is destined to be remembered as the villain who killed Hamilton ("The World Was Wide Enough"). The musical closes with a reflection on historical memory. Jefferson and Madison reflect on Hamilton's legacy, as Eliza tells how she keeps Hamilton's legacy alive through interviewing war veterans, getting help from Angelica, raising funds for the Washington Monument, speaking out against slavery, and establishing the first private orphanage in New York City ("Who Lives, Who Dies, Who Tells Your Story"). The musical ends with Hamilton shaking Eliza's hand. Eliza then turns towards the audience and lets out a tearful gasp.