The Plague is a novel about a plague epidemic in the large Algerian city of Oran. In April, thousands of rats stagger into the open and die. When a mild hysteria grips the population, the newspapers begin clamoring for action. The authorities finally arrange for the daily collection and cremation of the rats. Soon thereafter, M. Michel, the concierge for the building where Dr. Rieux works, dies after falling ill with a strange fever. When a cluster of similar cases appears, Dr. Rieux's colleague, Castel, becomes certain that the illness is the bubonic plague. He and Dr. Rieux are forced to confront the indifference and denial of the authorities and other doctors in their attempts to urge quick, decisive action. Only after it becomes impossible to deny that a serious epidemic is ravaging Oran, do the authorities enact strict sanitation measures, placing the whole city under quarantine.
The public reacts to their sudden imprisonment with intense longing for absent loved ones. They indulge in selfish personal distress, convinced that their pain is unique in comparison to common suffering. Father Paneloux delivers a stern sermon, declaring that the plague is God's punishment for Oran's sins. Raymond Rambert endeavors to escape Oran to rejoin his wife in Paris, but the city's bureaucrats refuse to let him leave. He tries to escape by illegal means with the help of Cottard's criminal associates. Meanwhile, Rieux, Tarrou, and Grand doggedly battle the death and suffering wrought by the plague. Rambert finalizes his escape plan, but, after Tarrou tells him that Rieux is likewise separated from his wife, Rambert is ashamed to flee. He chooses to stay behind and help fight the epidemic. Cottard committed a crime (which he does not name) in the past, so he has lived in constant fear of arrest and punishment. He greets the plague epidemic with open arms because he no longer feels alone in his fearful suffering. He accumulates a great deal of wealth as a smuggler during the epidemic.
After the term of exile lasts several months, many of Oran's citizens lose their selfish obsession with personal suffering. They come to recognize the plague as a collective disaster that is everyone's concern. They confront their social responsibility and join the anti-plague efforts. When M. Othon's small son suffers a prolonged, excruciating death from the plague, Dr. Rieux shouts at Paneloux that he was an innocent victim. Paneloux, deeply shaken by the boy's death, delivers a second sermon that modifies the first. He declares that the inexplicable deaths of innocents force the Christian to choose between believing everything and believing nothing about God. When he falls ill, he refuses to consult a doctor, leaving his fate entirely in the hands of divine Providence. He dies clutching his crucifix, but the symptoms of his illness do not match those of the plague. Dr. Rieux records him as a "doubtful case."
When the epidemic ends, Cottard cannot cope. He begins randomly firing his gun into the street until he is captured by the police. Grand, having recovered from a bout of plague, vows to make a fresh start in life. Tarrou dies just as the epidemic is waning, but he battles with all his strength for his life, just as he helped Rieux battle for the lives of others. Rambert's wife joins him in Oran after the city gates are finally opened, but Dr. Rieux's own wife dies of a prolonged illness before she and her husband can be reunited. The public quickly returns to its old routine, but Rieux knows that the battle against the plague is never over because the bacillus microbe can lie dormant for years. The Plague is his chronicle of the scene of human suffering that all too many people are willing to forget.
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