Thirteen years after he left the Philippines, Crisostomo Ibarra returns as Simoun, a rich jeweler sporting a beard and blue-tinted glasses, and a confidant of the the Captain-General. Abandoning his idealism, he becomes a cynical saboteur, seeking revenge against the Spanish Philippines system responsible for his misfortunes by plotting a revolution. Simoun insinuates himself into Manila high society and influences every decision of the Captain-General to mismanage the country’s affairs so that a revolution will break out. He cynically sides with the upper classes, encouraging them to commit abuses against the masses so that the latter would be encouraged to revolt against the oppressive Spanish colonial regime. This time, he does not attempt to fight the authorities through legal means, but through violent revolution using the masses. Simoun has reasons for instigating a revolution. First is to rescue María Clara from the convent and second, to get rid of ills and evils of Philippine society. His true identity is discovered by a now grown-up Basilio while visiting the grave of his mother, Sisa, as Simoun was digging near the grave site for his buried treasures. Simoun spares Basilio’s life and asks him to join in his planned revolution against the government, egging him on by bringing up the tragic misfortunes of the latter's family. Basilio declines the offer as he still hopes that the country’s condition will improve.
Basilio, at this point, is a graduating student of medicine at the Ateneo Municipal de Manila. After the death of his mother, Sisa, and the disappearance of his younger brother, Crispín, Basilio heeded the advice of the dying boatman, Elías, and traveled to Manila to study. Basilio was adopted by Captain Tiago after María Clara entered the convent. With Captain Tiago’s help, Basilio was able to go to Colegio de San Juan de Letrán where, at first, he is frowned upon by his peers and teachers not only because of the color of his skin but also because of his shabby appearance which he also experiences at Ateneo. Captain Tiago’s confessor, Father Irene is making Captain Tiago’s health worse by giving him opium even as Basilio tries hard to prevent Captain Tiago from smoking it. He and other students want to establish a Spanish language academy so that they can learn to speak and write Spanish despite the opposition from the Dominican friars of the Universidad de Santo Tomás. With the help of a reluctant Father Irene as their mediator and Don Custodio’s decision, the academy is established; however they will only serve as caretakers of the school not as the teachers. Dejected and defeated, they hold a mock celebration at apancitería while a spy for the friars witnesses the proceedings.
Simoun, for his part, keeps in close contact with the bandit group of Kabesang Tales, a former cabeza de barangay who suffered misfortunes at the hands of the friars. Once a farmer owning a prosperous sugarcane plantation and a cabeza de barangay (barangay head), he was forced to give everything to the greedy and unscrupulous Spanish friars. His son, Tano, who became a civil guard was captured by bandits; his daughter Hulî had to work as a maid to get enough ransom money for his freedom; and his father, Tandang Selo, suffered a stroke and became mute. Before joining the bandits, Tales took Simoun’s revolver while Simoun was staying at his house for the night. As payment, Tales leaves a locket that once belonged to María Clara. To further strengthen the revolution, Simoun has Quiroga, a Chinese man hoping to be appointed consul to the Philippines, smuggle weapons into the country using Quiroga’s bazaar as a front. Simoun wishes to attack during a stage play with all of his enemies in attendance. He, however, abruptly aborts the attack when he learns from Basilio that María Clara had died earlier that day in the convent.
A few days after the mock celebration by the students, the people are agitated when disturbing posters are found displayed around the city. The authorities accuse the students present at the pancitería of agitation and disturbing peace and has them arrested. Basilio, although not present at the mock celebration, is also arrested. Captain Tiago dies after learning of the incident and as stated in his will—forged by Irene, all his possessions are given to the Church, leaving nothing for Basilio. Basilio is left in prison as the other students are released. A high official tries to intervene for the release of Basilio but the Captain-General, bearing grudges against the high official, coerces him to tender his resignation. Julî, Basilio’s girlfriend and the daughter of Kabesang Tales, tries to ask Father Camorra’s help upon the advice of an elder woman. Instead of helping Julî, however, the priest tries to rape her as he has long-hidden desires for Julî. Julî, rather than submit to the will of the friar, jumps over the balcony to her death.
Basilio is soon released with the help of Simoun. Basilio, now a changed man, and after hearing about Julî's suicide, finally joins Simoun’s revolution. Simoun then tells Basilio his plan at the wedding of Paulita Gómez and Juanito, Basilio’s hunch-backed classmate. His plan was to conceal an explosive inside a pomegranate-styled Kerosene lamp that Simoun will give to the newlyweds as a gift during the wedding reception. The reception will take place at the former home of the late Captain Tiago, which was now filled with explosives planted by Simoun. According to Simoun, the lamp will stay lighted for only 20 minutes before it flickers; if someone attempts to turn the wick, it will explode and kill everyone—important members of civil society and the Church hierarchy—inside the house. Basilio has a change of heart and attempts to warn Isagani, his friend and the former boyfriend of Paulita. Simoun leaves the reception early as planned and leaves a note behind;
"Mene Thecel Phares."
Juan Crisostomo Ibarra.
Initially thinking that it was simply a bad joke, Father Salví recognizes the handwriting and confirms that it was indeed Ibarra’s. As people begin to panic, the lamp flickers. Father Irene tries to turn the wick up when Isagani, due to his undying love for Paulita, bursts in the room and throws the lamp into the river, sabotaging Simoun's plans. He escapes by diving into the river as guards chase after him. He later regrets his impulsive action because he had contradicted his own belief that he loved his nation more than Paulita and that the explosion and revolution could have fulfilled his ideals for Filipino society.
Simoun, now unmasked as the perpetrator of the attempted arson and failed revolution, becomes a fugitive. Wounded and exhausted after he was shot by the pursuing Guardia Civil, he seeks shelter at the home of Father Florentino, Isagani’s uncle, and comes under the care of doctor Tiburcio de Espadaña, Doña Victorina's husband, who was also hiding at the house. Simoun takes poison in order for him not to be captured alive. Before he dies, he reveals his real identity to Florentino while they exchange thoughts about the failure of his revolution and why God forsook him. Florentino opines that God did not forsake him and that his plans were not for the greater good but for personal gain. Simoun, finally accepting Florentino’s explanation, squeezes his hand and dies. Florentino then takes Simoun’s remaining jewels and throws them into the Pacific Ocean with the corals hoping that they would not be used by the greedy, and that when the time came that it would be used for the greater good, when the nation would be finally deserving liberty for themselves, the sea would reveal the treasures.
Below are some of the major and minor characters in the novel.
- Jomari Mercado - Crisóstomo Ibarra disguised as a wealthy jeweler, bent on starting a revolution to get revenge on the people who had accused him wrongly. Disguised as the top adviser of the Captain-General.
- Basilio - The eldest of Sisa's two sons, now an aspiring doctor whose medical education was being financed by Capitan Tiago. He is now at the point of graduation during the events in the novel.
- Isagani - Poet and Basilio's best friend; portrayed as emotional and reactive; Paulita Gómez' boyfriend before being dumped for fellow student Juanito Peláez
- Kabesang Tales - Telesforo Juan de Dios, a former cabeza de barangay(barangay head) of Sagpang, a barangay in San Diego's neighboring town Tiani, who resurfaced as the feared Luzón bandit Matanglawin (Tagalog for "Hawkeye");
- Don Custodio - Custodio de Salazar y Sánchez de Monteredondo, a famous "journalist" who was asked by the students about his decision for the Academia de Castellano. In reality, he is quite an ordinary fellow who married a rich woman in order to be a member of Manila's high society.
- Paulita Gomez - The girlfriend of Isagani and the niece of Doña Victorina, the old Indio who passes herself off as a Peninsular, who is the wife of the quack doctor Tiburcio de Espadaña. In the end, she and Juanito Peláez are wed, and she dumps Isagani, believing that she will have no future if she marries him.
- Macaraig - One of Isagani's classmates at the University of Santo Tomas. He is a rich student and serves as the leader of the students yearning to build the Academia de Castellano.
- Father Florentino - Isagani's godfather, and a secular priest; was engaged to be married, but chose to be a priest after being pressured by his mother, the story hinting at the ambivalence of his decision as he chooses an assignment to a remote place, living in solitude near the sea.
- Juli - Juliana de Dios, the girlfriend of Basilio, and the youngest daughter of Kabesang Tales. To claim her father from the bandits, she had to work as a maid under the supervision of Hermana Penchang. Eventually, she was freed but committed suicide after Father Camorra attempted to rape her.
- Juanito Pelaez - The son of Don Timoteo Pelaez, a Spanish businessman, he is also one of the members of Macaraig's gang who wish to have the Academia de Castellano built. He is considered by Isagani as his rival to Paulita Gomez, the woman whom he fell in love and wed in the end. Placido Penitente considers him as a "good for nothing" classmate.
- Doña Victorina - Victorina delos Reyes de Espadaña, known in Noli Me Tangere as Tiburcio de Espadaña's cruel wife. She is the aunt of Paulita Gomez, and favors Juanito Pelaez than Isagani. Although of Indio ideology, she considers herself as one of the Peninsular.
- Father Camorra - The parish priest of Tiani, San Diego's adjacent town. He has been desiring young women ever since. He nearly raped Juli causing the latter to commit suicide.
- Ben-Zayb - The pseudonym of Abraham Ibañez, a journalist who believes he is the "only" one thinking in the Philippines. (Ben-Zayb is an anagram of Ybanez, an alternate spelling of his name.)
- Placido Penitente - A student of the University of Santo Tomas who was very intelligent and wise but did not want, if not only by his mother's plea, to pursue his studies. He also controls his temper against Padre Millon, his physics teacher.
- Hermana Penchang - Sagpang's rich pusakal (gambler). She offers Huli to be her maid so the latter can obtain money to free Kabesang Tales. Disbelieving of Huli and her close friends, she considers herself as an ally of the friars.
- Karl Ong - Don Tiburcio is Victorina de Espadaña's lame husband. He is currently on hiding with Father Florentino.
- Father Írenë - Captain Tiago's spiritual adviser. Although reluctant, he helped the students to establish the Academia de Castellano after being convinced by giving him achestnut. The only witness to Captain Tiago's death, he forged the last will and testament of the latter so Basilio will obtain nothing from the inheritance.
- Quiroga - A Chinese businessman who dreamed of being a consul for his country in the Philippines. He hid Simoun's weapons inside his house.
- Loie Tabiliran - Juanito's father. He is a rich businessmen and arranges a wedding for his son and Paulita. He and Simoun became business partners.
- Ivan Paul Tano - Father of Kabesang Tales. He raised the sick and young Basilio after he left their house in Noli me Tangere. He died in an encounter on the mountains with his son Tales.
- Father Fernández - The priest-friend of Isagani. He promised to Isagani that he and the other priests will give in to the students' demands.
- Sandoval - The vice-leader of Macaraig's gang. A Spanish classmate of Isagani, he coerces his fellow classmates to lead alongside him the opening of the Spanish language academy.
- Hermana Báli - Another gambler in Tiani. She became Huli's mother-figure and counselor; helped to release Kabesang Tales from the hands of bandits.
- Pasta - One of the great lawyers of mid-Hispanic Manila, opposed the students' demands for a Spanish language academy
- Father Millon - The Physics teacher of the University of Santo Tomas. He always becomes vindictive with Placido and always taunts him during class.
- Tadeo - Macaraig's classmate. He, along with the other three members of their gang, supposedly posted the posters that "thanked" Don Custodio and Father Irene for the opening of the Academia de Castellano.
- Leeds - An American who holds stage plays starring decapitated heads; he is in good friends with Simoun.
- Tano - Kabesang Tales's elder son after his older sister, Lucia died in childhood. He is currently one of the Guardia Civil. He then returned under the name Carolino after his exile in Caroline Islands.
- Pepay - Don Custodio's supposed "girlfriend". A dancer, she is always agitated of her "boyfriend"'s plans. She seems to be a close friend of Macaraig.
- Gobernador General - The highest-ranking official in the Philippines during the Spanish colonial period, this unnamed character pretends that what he is doing is for the good of the Indios, the local citizens of the country, but in reality, he prioritizes the needs of his fellow Spaniards living in the country.
- Pecson - Basilio's classmate who had no idea on the happenings occurring around him. He suggested that they held the mock celebration at the panciteria.
- Father Hernando de la Sibyla- A Dominican friar introduced in Noli Me Tangere, now the vice-rector of the University of Santo Tomas.
- Father Bernardo Salvi- Former parish priest of San Diego, now the director and chaplain of the Santa Clara convent.
- Captain Tiago - Santiago delos Santos, although making a cameo appearance, Captain Tiago is Maria Clara's father and the foster-father to Basilio. His health disintegrates gradually because of the opium he was forced to smoke given to him by Father Irene.
- Maria Clara - Introduced in Dr. Rizal's first novel "Noli Me Tangere". She was once the girlfriend of Crisostomo Ibarra but chose to became a nun despite Father Damaso's arguments. She eventually passed away, as witnessed by Basilio when he visited the convent of Santa Clara; this propelled Simoun to expedite his plans for revolution.