Lieutenant Frederic Henry is a young American ambulance driver serving in the Italian army during World War I. At the beginning of the novel, the war is winding down with the onset of winter, and Henry arranges to tour Italy. The following spring, upon his return to the front, Henry meets Catherine Barkley, an English nurse’s aide at the nearby British hospital and the love interest of his friend Rinaldi. Rinaldi, however, quickly fades from the picture as Catherine and Henry become involved in an elaborate game of seduction. Grieving the recent death of her fiancé, Catherine longs for love so deeply that she will settle for the illusion of it. Her passion, even though pretended, wakens a desire for emotional interaction in Henry, whom the war has left coolly detached and numb.

When Henry is wounded on the battlefield, he is brought to a hospital in Milan to recover. Several doctors recommend that he stay in bed for six months and then undergo a necessary operation on his knee. Unable to accept such a long period of recovery, Henry finds a bold, garrulous surgeon named Dr. Valentini who agrees to operate immediately. Henry learns happily that Catherine has been transferred to Milan and begins his recuperation under her care. During the following months, his relationship with Catherine intensifies. No longer simply a game in which they exchange empty promises and playful kisses, their love becomes powerful and real. As the lines between scripted and genuine emotions begin to blur, Henry and Catherine become tangled in their love for each other.

Once Henry’s damaged leg has healed, the army grants him three weeks convalescence leave, after which he is scheduled to return to the front. He tries to plan a trip with Catherine, who reveals to him that she is pregnant. The following day, Henry is diagnosed with jaundice, and Miss Van Campen, the superintendent of the hospital, accuses him of bringing the disease on himself through excessive drinking. Believing Henry’s illness to be an attempt to avoid his duty as a serviceman, Miss Van Campen has Henry’s leave revoked, and he is sent to the front once the jaundice has cleared. As they part, Catherine and Henry pledge their mutual devotion.

Henry travels to the front, where Italian forces are losing ground and manpower daily. Soon after Henry’s arrival, a bombardment begins. When word comes that German troops are breaking through the Italian lines, the Allied forces prepare to retreat. Henry leads his team of ambulance drivers into the great column of evacuating troops. The men pick up two engineering sergeants and two frightened young girls on their way. Henry and his drivers then decide to leave the column and take secondary roads, which they assume will be faster. When one of their vehicles bogs down in the mud, Henry orders the two engineers to help in the effort to free the vehicle. When they refuse, he shoots one of them. The drivers continue in the other trucks until they get stuck again. They send off the young girls and continue on foot toward Udine. As they march, one of the drivers is shot dead by the easily frightened rear guard of the Italian army. Another driver marches off to surrender himself, while Henry and the remaining driver seek refuge at a farmhouse. When they rejoin the retreat the following day, chaos has broken out: soldiers, angered by the Italian defeat, pull commanding officers from the melee and execute them on sight. The battle police seize Henry, who, at a crucial moment, breaks away and dives into the river. After swimming a safe distance downstream, Henry boards a train bound for Milan. He hides beneath a tarp that covers stockpiled artillery, thinking that his obligations to the war effort are over and dreaming of his return to Catherine.

Henry reunites with Catherine in the town of Stresa. From there, the two escape to safety in Switzerland, rowing all night in a tiny borrowed boat. They settle happily in a lovely alpine town called Montreux and agree to put the war behind them forever. Although Henry is sometimes plagued by guilt for abandoning the men on the front, the two succeed in living a beautiful, peaceful life. When spring arrives, the couple moves to Lausanne so that they can be closer to the hospital. Early one morning, Catherine goes into labor. The delivery is exceptionally painful and complicated. Catherine delivers a stillborn baby boy and, later that night, dies of a hemorrhage. Henry stays at her side until she is gone. He attempts to say goodbye but cannot. He walks back to his hotel in the rain.