The story takes place in Genoa in the middle of the 14th century. The Republic of Genoa is about to elect a doge. The nominee of the plebeian popular leaders Pietro and Paolo is Simon Boccanegra, who has successfully cleared the harbour of pirate ships. Boccanegra has so far rejected the position. However, his beloved Maria is being kept prisoner in the castle of her tyrannical father, Fiesco. Even though Maria has borne Boccanegra a baby girl, her aristocratic father opposes his relationship with his daughter, deeming him too lowly in station to marry her. For this reason, he has even separated the child from her mother. Pietro and his comrades succeed in getting Boccanegra to assume the post of governor after all: this way he cannot be denied Maria's hand in marriage.
In the square in front of the palace, Fiesco is mourning his dead daughter in loving sorrow and grief when he encounters Boccenegra, who believes that his victories in battle merit him the young noblewoman's hand. Fiesco, however, fears that Boccanegra is trying to also take control of the city away from him and swears revenge on him. Fiesco asks Boccanegra to bring him his illegitimate daughter, his own granddaughter, so that he can raise her in a manner befitting her rank. If Boccanegra complies, he will pardon him. Boccanegra, however, is unable to fulfil this request, as the girl has been abducted: she has vanished without a trace.
Left alone, Boccanegra summons up all his courage to enter the palace to see his beloved again. But instead of a joyous reunion, he finds the dead young woman laid out on a bier.
Meanwhile, the deliriously overjoyed people call out the name of the new doge: “Boccanegra”. Fiesco flees.
Twenty-five years later, while waiting for her beloved in the Grimaldi palace not far from Genoa, Amelia broods over a sorrowful memory: long ago she was abducted and brought to this wealthy home by a strange woman. She is interrupted by the arrival of Gabriel Adorno, the young patrician with whom she is in love. Amelia is afraid for him, because he has helped incite the revolt and therefore is now in danger.
An emissary arrives: it is Pietro announcing the arrival of the doge. He has come to ask to have the girl married to Paolo, a confidante of his. Gabriele sends for a monk, so that he can quickly give his blessing to the marriage to the girl.
The monk – who is really Fiesco – appears and reveals Amelia's secret: she was of low birth, and the childless Countess Grimaldi abducted her when she was a little child. Later on, shortly before she died, the countess made Amelia her heir. The monk gives his blessing to their union.
Boccanegra arrives with Paolo, but immediately sends him back when he receives news that the people are seething with discontent in Genoa.
The girl knows that Paolo only wants her for her wealth, so she tells Boccanegra her secret: she is not a Grimaldi by blood. The girl believes that her father is dead. Boccanegra feels a glimmer of hope and shows her a portrait of her mother. Before her death, Countess Grimaldi had shown the girl the same portrait of her real mother. Father and daughter are happily reunited. They swear to each other that they will keep their secret.
Boccanegra commands Paolo to withdraw his offer of marriage. Paolo assigns Pietro the task of abducting the girl.
The malcontents are getting ready to revolt against the doge. The people, however, turn against the rebels. Boccanegra calls for peace and is ready to make Paolo doge. Paolo, however, has pronounced a curse on the guilty and flees in horror.
Paolo decides that he must kill Boccanegra and mixes poison into his cup. He has Gabriele and Fiesco, who are imprisoned in the palace, brought before him and then offers Fiesco his freedom if he is willing to stab Boccanegra with a dagger. Fiesco, however, has nothing to say to the traitor. Paolo leads Gabriele to believe that the doge is keeping Amelia in the palace as his lover. Learning of this, Gabriele plots revenge against the doge. Just as he is lamenting her faithlessness and the loss of their love, in comes Amelia. Without revealing her secret, she tells Gabriele that her affection for the doge is holy and that Boccanegra is guilty of nothing. She assures Gabriele of her love. Upon hearing the doge's approaching footsteps, Amelia instructs Gabriele to hide. But even the girl is unable to dissuade him from his plan of killing Boccanegra.
Amelia reveals the name of her lover to her father. Since Gabriele has rebelled against him, he can show him no mercy either. The girl declares that if the doge has Gabriele killed, she will die along with her lover. After she has left, he drinks from the cup that Paolo has poisoned and immediately falls asleep. Gabriele emerges from his hiding place and is preparing to stab the sleeping doge when Amelia rushes in and manages to throw herself between the two men. Boccanegra awakens. Amelia is about to reveal her life's secret to her beloved, but the doge notices the dagger in the young man's hand and himself tells Gabriele that Amelia is his daughter. Dumbfounded, Gabriele feels that it would be a just punishment for the doge to kill him. But the doge is ready to die, if it means that there will be peace between the parties.
The crowd of rebels is approaching. Boccanegra asks Gabriele to convince the people to withdraw. Gabriele starts off, hoping that that the crowd will rejoice when the doge calls for peace. As a reward, the father promises his daughter to the youth, who rushes off to face the rebels.
A few hours later, the captain of the crossbowmen leads in Fiesco, who has been freed from prison. Then they bring in Paolo, clapped in fetters for having incited the rebellion that they have just quashed. Boccanegra sentences him to death, and he is led away by the executioner. Amelia and Gabriele are accompanied by a bridal procession. Fiesco emerges from his place of concealment, ready to wreak his revenge. Boccanagre admonishes him, reminding him that he once promised him peace if he handed over his daughter. Now he reveals that his daughter is none other than Amelia Grimaldi. The two men reconcile. Fiesco reveals that the doge's drink was poisoned by a traitor. Unafraid of death, Boccanegra embraces Fiesco one last time and reveals to Amelia that Fiesco is the father of her departed mother. Boccanegra bids farewell to his daughter. His final acts are to confer a blessing on his child and to install Gabriele as the next governor.