At the start of Book I, Art arrives at his father Vladek’s home in order to record his father’s Holocaust memories for a book he plans to write about his father’s life. Vladek begins his story with his life as a young man in Sosnowiec, Poland, in the years leading up to World War II. He meets and marries Anja Zylberberg, a young, intelligent woman from a well-to-do family who helps him to found his own textile factory.
After the birth of their son, Richieu, Anja suffers from a severe attack of post-partum depression, and Vladek accompanies her to a sanitarium in Czechoslovakia, where she will receive medical treatment. On the way there, they witness the spread of Nazism and anti-Semitism throughout central Europe, but are still relatively safe from it in Czechoslovakia. Anja recovers, and they return to Poland. Vladek discovers that in his absence, his factory was vandalized, an ominous foreshadowing of the violence to come.
With the onset of World War II, Vladek leaves for the front as a Polish soldier, where he is taken as a prisoner of war by the Germans. When he is finally released from the POW camp, he returns to a Poland, which is now occupied by the Germans, who extend their anti-Semitic policies there. Vladek loses his factory, but does what he can to make a living on the black market.
Gradually, Jews are taken from his hometown to the camps, including Anja’s elderly grandparents. After being moved to a ghetto, Vladek, Anja, and their family are taken to Dienst Stadium, where Vladek’s father, sister, and his sister’s children are all deported to the camps. Vladek, Anja, and other members of their family are sent with the rest of Sosnowiec’s Jews to Srodula. Vladek and Anja send their son, Richieu, to stay with a relative in another Polish town for safekeeping, but they find out later that the Jews there are also deported to the camps.
In order to avoid deportation, Anja’s sister Tosha commits suicide and poisons Richieu and her own children. When it becomes clear that the Germans intend to send the rest of the Sosnowiec Jews to the camps, Vladek and Anja go into hiding on a farm outside Sosnowiec. They pay smugglers to transport them out of Poland into Hungary, but the smugglers turn them over to the Germans.
Vladek is taken to Auschwitz, while Anja is taken to Birkenau. Conditions are terrible at these camps, but Vladek is able to survive by marketing his skills as a tin worker and a shoemaker. He is also able to save enough rations to barter Anja’s transfer to Auschwitz from Birkenau. They spend a year in the camps until, with the Allies on the horizon, the Germans decide to disassemble the camps and finish executing the Jews at different camps within Germany.
Vladek ends up in Dachau, where conditions are even worse than in Auschwitz, and catches typhus fever. He is then transported with other prisoners to the Swiss border, where they expect to be freed. But the German soldiers escort them into the woods, apparently to execute them. The German soldiers run away before they carry out their plan, afraid of repercussions by the American soldiers.
After another narrow escape, Vladek and his fellow prisoner and friend Shivek hide in a farmhouse until the American soldiers finally take over the town. Vladek returns to Sosnowiec, where he reunites with Anja. They emigrate first to Sweden, and then to the United States, where they begin a new life and a new family with the birth of Art, their second son.
Running parallel to Vladek’s personal history is the story of Art’s writing the novel, complicated by his tense relationship with his father. Art still experiences unresolved anger and depression over his mother’s suicide in 1968, and some of those feelings are directed at Vladek, who he views as partly complicit in her death. Vladek has remarried and his second wife, Mala, is also a Holocaust survivor, but they constantly bicker over money. At the end of Book I, Art is infuriated to learn that Vladek destroyed all of Anja’s diaries from the war.
Book II begins with Art considering the critical and commercial success of Book I. As he begins to relate the story of Vladek’s life in Auschwitz, Art also reflects on his conflicted feelings about writing about the Holocaust, and talks with his therapist about his relationship with his father. Art and his wife Françoise’s vacation is interrupted when they receive a call from Vladek, who tells them that Mala has left him, taking a good chunk of their money with her.
Mala and Vladek eventually reunite, and they move to Florida together. In Florida, Vladek’s health worsens, and Art flies to Florida to accompany his father back to a hospital in New York. While Vladek recovers temporarily, his heart condition worsens. The novel ends when Vladek finishes telling Art about his reunion with Anja in Sosnowiec.