The film is based on the events that happened on the ship Exodus in 1947 and dealing with the founding of the state of Israel around 1948.
Nurse Katherine (Kitty) Fremont (Eva Marie Saint) is an American volunteer nurse at the Karaolos detention camp in Cyprus, where thousands of Jews - Holocaust survivors - are being held, as they have no homeland to return to. They sit in anticipation of the day they will be liberated. Ari Ben Canaan (Paul Newman), a Haganah rebel who previously was a Captain in the Jewish Brigade of the British Army in World War II, obtains a cargo ship and is able to smuggle 611 Jewish inmates out of the camp for an illegal voyage to Palestine before being found out by military authorities. When the British discover that the refugees are in a ship in the harbor of Famagusta, they blockade the harbor. The refugees stage a hunger strike, during which the camp's doctor dies; then the British relent and allow the Exodus safe passage.
Meanwhile, Kitty has grown very fond of Karen Hansen (Jill Haworth), a young Danish-Jewish girl searching for her father, from whom she was separated during the war. She has taken up the Zionist cause, much to the chagrin of Kitty, who had hoped to take young Karen to America so that she can begin a new life there.
Meanwhile, opposition to the partition of Palestine into Arab and Jewish states is heating up, and Karen's young beau Dov Landau (Sal Mineo) proclaims his desire to join the Irgun, a radical Zionist underground network. Dov goes to an Irgun address, only to get caught in a police trap. After he is freed, he is contacted by members of the real Irgun. Dov is interviewed by Ari Ben Canaan's uncle Akiva (David Opatoshu). Before swearing Dov in, Akiva forces the boy to confess that he was a Sonderkommando in Auschwitz and that he was raped by Nazis. Because of his activities, Akiva has been disowned by Ari's father, Barak (Lee J. Cobb), who heads the mainstream Jewish Agency trying to create a Jewish state through political and diplomatic means. He fears that the Irgun will damage his efforts, especially since the British have put a price on Akiva's head. When Dov successfully bombs the King David Hotel in an act of terrorism, leading to dozens of fatalities, Akiva is arrested and sentenced to hang. Meanwhile, Karen's father has been found, but he is suffering from clinical depression and does not recognize her. Karen has gone to live at Gan Dafna, the Jewish kibbutz near Mount Tabor at which Ari was raised.
Kitty and Ari have fallen in love, but Uncle Akiva's imprisonment is an obstacle, and Ari must devise a plan to free the prisoners.
Dov Landau, who had managed to elude the arresting soldiers, turns himself in so that he can use his knowledge of explosives to rig the Acre prison and plan an escape route. All goes according to plan; hundreds of prisoners, including Akiva, manage to escape. But Akiva is fatally shot by British soldiers while evading a roadblock set up to catch the escaped prisoners. Ari, who was driving, is badly wounded. He makes his way to Abu Yesha, an Arab village where his lifelong friend, Taha, is the mukhtar. Kitty is brought there and treats his wound.
An independent Israel is now in plain view, but Arab nationals commanded by the Grand Mufti of Jerusalem plot to attack Gan Dafna and kill its villagers. Ari receives prior warning of this attack from Taha, and he manages to get the children of the town out in a mass overnight escape. Karen, ecstatic over the prospect of a new nation, searches and finds Dov (who was patrolling outside the town) proclaims her love for him, and traveled back to Gan Dafna, only to be captured and killed by a wandering Arab. In the morning, Dov and a patrol group finds her lifeless body. That same day, the body of Taha is found hanging in his village killed by Arab extremists with a Star of David symbol carved on his body. Karen and Taha are buried together in one grave. At the Jewish burial ceremony, Ari swears on their bodies that someday, Jews and Arabs will live together and share the land in peace. The movie then ends with Ari, Kitty, and a Palmach contingent entering trucks and heading toward battle.