After a brief "Prelude," the lights come on Prince Metternich, the five Rothschild sons, and their mother, Gutele Rothschild. We are in Frankfurt in 1818. Prince Metternich has apparently suffered a defeat and has come to make terms with the Rothschilds. But he warns them that their newfound power will not change the world for the better; it will only change them. Gutele assures him that her sons will not change. They have the past to remind them of who they are and what they stand for.

The scene shifts to the entrance to the Frankfurt ghetto in 1772. We hear the Town Crier proclaiming that "the ghetto is closing" ("Town Crier's Chant 1"). Mayer Rothschild, returning from Hanover, hurries in. Before he can enter the ghetto, he is humiliated by several teenagers. When they chant: "Jew, Do Your Duty," he knows that he must remove his hate and bow, which he does. Before he can enter the ghetto, he is further humiliated: he finds that he must bribe the ghetto guard to let him into the ghetto.

Mayer enters his shop where his fiancée, Gutele, waits for him. She expects that they will return to Hanover where they will marry. To her dismay, Mayer tells that he has come back to live and work in Frankfurt. She is upset because in Frankfurt only a few Jews are allowed to marry every year, so there is no telling when they can be married. Mayer tells her that he can make a better living in Frankfurt. She assures him that she needs very little to content ("One Room").

Not only does Mayer intend to work in his shop; he also intends to sell rare coins at the Frankfurt Fair. As he sings "He Tossed a Coin," the scene shifts to the Frankfurt Fair. One of his customers is Princes William of Hesse. By giving Prince William the gift of a rare coin, Mayer ingratiates himself with the Prince, who gives him permission to marry. The Prince's secretary, Budurus, gives Mayer the marriage grant.

Mayer realizes that Budurus could help him gain entry to William's Court, with the possibility of doing business there. Budurus sees that his relationship with Mayer might be mutually beneficial but warns Mayer of how he can expect to be treated at Court ("Pleasure and Privilege").

Mayer needs allies in his struggle to succeed in a hard world, where his humble origins and despised religion are a detriment to any success. He knows that the most trustworthy allies he can have would be his sons.

We witness his fives sons - Amshel, Salomon, Nathan, Jacob, and Kalmann - being born ("Sons"). When the boys reach their adolescence they begin work in the family shop. As has happened before, a drunken mob invades the ghetto, and the family is forced to hide in the cellar. A troubled Mayer ponders how to stop the humiliation and danger that his family is forced to endure. "What's to be Done?" he asks himself, and determines that only great wealth can protect them from the hatred and violence of the outside world. After the mob has wrecked the shop and the boys - now then years older - survey the damage, Gutele tries to comfort them. "We have enough," she assures them. But they demand all the freedom "other men aspire to." ("Everything")

Mayer's sons study banking, hoping for some opportunity that will put them on the road to success. The opportunity arises when Prince William's uncle, the King of Denmark, needs money. William is eager to loan it to him; but as he comments, "Loans to relatives have a way of degenerating into gifts." Consequently, he wants his loan to be handled by bankers who seem to have no connection with him. Budurus presents Rothschild and his sons to the Prince as the appropriate bankers. At first, William refuses to deal with "Jewish peddlers" but the Rothschilds' intelligence and audacity win him over. The Rothschilds celebrate ("Rothschild and Sons").

On their return from Denmark, they find that Napoleon has invaded Hesse and Prince William has fled. Budurus wants Mayer to hide William's account books in his cellar. Instead, Mayer chooses to send his sons around Europe to collect William's debts ("The Sons Depart"). Gutele is heartsick as her sons leave, knowing that they must travel through wartorn Europe. After her sons have left, she looks at a map of Europe and, in her anguish, sings "Just a Map."

Nathan Rothschild arrives in "This Amazing London Town" and promptly makes an unwise investment. To prevent this from happening again, Mayer and his other sons organize a courier service to relay information to one another. By using the information he receives, Nathan is able to redeem himself and become the envy of the other banker-brokers. The Rothschild family has become so wealthy that the Lord Herries, the Chancellor of the Exchequer, asks Nathan to loan the British government money so they can prosecute the war against Napoleon. Although Mayer thinks that such a loan would be both imprudent and dangerous, Nathan wants to make it. This leads to an argument so bitter ("He Never Listens") that Mayer seriously considers banishing Nathan from the Rothschild family. Gutele persuades Mayer otherwise ("Sons (Reprise)"). Mayer then consults all his sons and they agree that family should make the loan on condition that Prince Metternich, head of the allied restrictions on the Jewish people in their lands. Metternich agrees. Hearing this news, Mayer is deeply moved ("In My Own Lifetime").

At the Congress at Aix-la-Chapelle, Prince Metternich celebrates the defeat of Napoleon and the return of the status quo ("Stability"). Mayer and Nathan attend the Congress to obtain the Declaration of Rights for European Jews. They are shocked to learn that Metternich and his allies have no intention of honoring their agreement. Mayer returns to Frankfurt desolate and feeling that he has failed. Aware that he is dying, he summons his sons.

After Mayer's funeral, Gutele and her sons gather in Frankfurt. Nathan has learned that Metternich and his allies plan to release a new bond issue at a price that will undercut the price of the bond the Rothschilds have issues. In Nathan's words: "We helped them win the war. Now they intend to destroy us." Nathan urges his brothers to fight back by lowering the price of their own bonds. His brothers regard this as suicidal. But when they ask Gutele what she wants, she concurs with Nathan. To defeat Metternich, she is willing to risk the entire Rothschild fortune ("Everything (Reprise)").

The final scene is a return to the very beginning. The Rothschilds have defeated Metternich and obtained the Declaration of Rights for European Jews. But they know that life will continue to be difficult in a world that is never free of prejudice and the scapegoating of minorities. They are joined by Mayer Rothschild, whose spirit is still very much alive to them ("In My Own Lifetime (Finale)").