The novel begins with Yossarian faking a liver ailment in order to stay at the hospital and avoid going back into combat. While Yossarian is there, the chaplain visits him and likes him. The chaplain is also comfortable talking to him as well, and Yossarian invites him to come back again. The narrator then introduces a wide-ranging cast of characters, which include: Clevinger, a Harvard graduate who ends up mysteriously disappearing while flying; Orr, Yossarian’s crafty roommate; Milo, a mess officer who eventually creates a successful business; Havemeyer, who enjoys the danger of the missions; McWatt, who loves flying dangerously low; Nately, who is the son of a wealthy businessman and has fallen in love with a prostitute in Rome; and Chief White Halfoat, a Native American officer who is determined to die of pneumonia. Yossarian goes to ask Doc Daneeka to ground him, but he refuses and tells him that it’s because of Catch-22. Doc Daneeka says that those who are insane can be grounded if they ask, but because Yossarian asked it shows that he is sane enough to fly. Only those who are willing to continue flying are the ones who are crazy enough to be grounded.While General Dreedle and Peckem quarrel against each other and do not care about winning the war at all, Colonel Cathcart continually increases the number of missions that his men are required to fly.
Being in his squadron, Yossarian finds this to be unfair as other squadrons are not required to do so, Cathcart and his assistant, Colonel Korn, do not care. Colonel Cathcart is concerned with being promoted to a general while Colonel Korn is focused on being promoted to be a full colonel. Cathcart volunteers his men to fly a dangerous mission to Bologna, and Yossarian tries to avoid the mission for as long as possible.
However, Yossarian ends up flying there anyway and barely manages to survive as his plane as his plane is constantly bombarded with flak. After the mission, Yossarian quickly leaves to Rome and briefly spends the night with Luciana.As the story progresses, unfortunate events continue to happen as characters begin to disappear or die. Dunbar disappears after causing havoc in the hospital another time, McWatt flies into a mountain after accidentally killing Kid Sampson by flying his plane too low to the lake, and Nately, Dobbs, and Havermeyer are killed during their mission to La Spezia. The chaplain is devastated to hear about these disappearances and deaths becoming more frequent. He also sees the toll the increasing number of missions on Yossarian and goes to meet with higher officials like Colonel Korn and Cathcart.
However, they ignore his requests, and eventually, the chaplain is even tried and investigated for the case of forging “Washington Irving” on official documents. He is eventually set free, but as time goes on his faith in God begins to be questioned. He finally decides to believe in God and continue by standing up to his superiors in order to help Yossarian and the other soldiers.
After seeing his friends disappear one by one, Yossarian begins to change his views. In the beginning, he was satisfied by avoiding his own duties. However, as the story progresses he begins to feel that the raised number of missions are unnecessary, especially that the war is near the end. After going back to Rome for a final visit and seeing it in total destruction, Yossarian decides to no longer fly missions.
Many of the soldiers begin to hear about this, so Colonel Cathcart and Korn strike him a deal: either be grounded and pretend to like them or be court-martialed and put in jail. Although Yossarian originally accepts the offer, the chaplain is able to talk him out of it. The chaplain also brings him the news of Orr successfully escaping to Sweden. With this news, Yossarian decides that the best course for him is to flee to Sweden as well. After talking with Major Danby and the chaplain, the novel ends with him running out the door to Sweden.