Narrated in the third person by an unnamed narrator, Refugee opens with a scene from the point of view of Josef Landau, a twelve-year-old German-Jewish boy living with his mother, father, and little sister in Berlin. On November 9, 1938, a night that would become known as Kristallnacht, Nazi Brownshirts break into his home and arrest his father, Aaron, for continuing to practice law despite an anti-Semitic policy barring him from the profession.
Aaron spends six months in the Dachau concentration camp before being released on the condition that he leave Germany. The Landaus board a ship bound for Cuba, where they and more than 900 other Jewish refugees aboard the MS St. Louis have been granted visas. While Josef and Ruthie enjoy being on board the St. Louis, where they are free to play with other children and are treated even by the German stewards as regular people, Aaron lives with the trauma of what he endured at Dachau. Paranoid, he won't leave his cabin, believing the Nazis are laying traps for him. Josef also encounters an officer named Schiendick, who is openly anti-Semitic toward him.
Upon arrival in a Cuban harbor, the passengers are subjected to a medical examination. After passing, they are told they will be able to go on land tomorrow. "Mañana" becomes a daily refrain as the refugees are held in limbo for over a week. As tensions rise, Schiendick ransacks the Landaus' room, and Aaron tries to commit suicide by jumping ship. He is rescued and brought to a hospital on land, where he is sedated. The passengers then learn they are being denied entry into Cuba. While Aaron stays in Cuba, the other Landaus travel back across the Atlantic, denied entry into the US as well.
The passengers are divided up among several European countries and England. Josef and his mother and sister settle in France, but have to move into hiding when the Nazis invade ten months later. The storyline ends with Rachel trying to buy her children's freedom from Nazi soldiers. They say she can only free one child. Josef volunteers to accompany his mother to a concentration camp, and Ruthie is left in the woods of the French countryside.
In the second storyline, twelve-year-old Isabel Fernandez lives in Cuba in 1994. She and most other common people are starving due to the fall of the Soviet Union, which had been supporting the communist nation, and a US embargo that prevents countries from trading with Cuba. When her father is nearly arrested in a riot in the center of Havana, Isabel and her family join their neighbors in fleeing the country by boat. Isabel trades her trumpet for the two cans of gasoline needed for the trip. The US has a policy at the time that means Cuban refugees can become naturalized if they arrive on US soil; if they are caught in the water while making the crossing, however, they will be detained at Guantanamo Bay and likely be sent back to Cuba.
The crossing from Cuba to Florida is perilous in the homemade boat, which uses a modified motorcycle engine and is ill-equipped to carry nine passengers. The group accidentally drifts to the Bahamas, where they are given supplies by sympathetic tourists but are legally barred from landing. On the journey north, Isabel's young neighbor Iván dies from a shark bite and her mother goes into labor.
The refugees are about to be captured by the US Coast Guard when Isabel's grandfather sacrifices himself by jumping in the water and attracting their attention. Isabel runs onto land with her newborn brother held aloft. Her storyline ends several months later: having gotten a new trumpet, Isabel plays a salsa version of "The Star-Spangled Banner," mixing Cuban and American cultures.
The third storyline follows Mahmoud Bishara, who is also twelve. Living in Aleppo in 2015, Mahmoud and his family have been considering leaving their country since the outbreak of the Syrian Civil War in 2011. When a bomb blows away one wall of their apartment building, the Bisharas begin the drive to Turkey, their ultimate destination being Germany, an EU country that is accepting Syrian refugees.
The journey is fraught with danger, and the family must abandon their car when soldiers from one of the many warring factions fire at them. From Izmir, Turkey, the refugees wait for a smuggler to take them by boat to Greece—an EU country. The smuggler's rubber dinghy capsizes, leaving the Bisharas and other refugees stranded in the water at night with fake life jackets, sold to them by an opportunistic child in Turkey. When another refugee boat passes, Mahmoud and his mother grab on, passing Mahmoud's baby sister Hana to a woman on board.
The rest of the family wait in the water until the Greek Coast Guard rescues them and brings them to Lesbos, where Mahmoud sees piles of life jackets left by other refugees; there are also drowned bodies on the shore. Mahmoud's family moves through mainland Greece, Macedonia, Serbia, and Hungary, traveling by ferry, taxi, train, and on foot. They are held at gunpoint by a Serbian taxi driver, who robs them, and Mahmoud's father is beaten by Hungarian soldiers while in a detention camp. All the while, they cannot find Hana.
At a refugee camp in Hungary, Mahmoud notices United Nations observers making a site visit. Knowing the Hungarian guard won't harm him while the UN is present, he leaves the gymnasium and begins walking toward Austria. The rest of the refugees follow him, and soon media are covering the procession. After twelve hours, the refugees arrive at the unguarded border and are welcomed by Austrians with food and supplies. Mahmoud and his family travel by train to Germany, where they declare they are seeking asylum.
After several weeks, the Bisharas go to stay with a host family in Berlin. It turns out to be an elderly Ruthie Landau. She explains that her brother sacrificed himself so she could live and take the Bisharas in. She says they will find Hana. The novel ends with Mahmoud looking at a picture of Josef and feeling grateful he has found a new home.
