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Former architecture student Frederic Henry, now a lieutenant in the Italian army's World War I ambulance service, spends his free time drinking and chasing women with his comrade, Captain Rinaldi.  On one of their outings, Frederic meets Catherine Barkley, an English nurse whose fiancée was killed in the war.  Rinaldi had arranged for Frederic to be paired with Catherine's friend, nurse Helen Ferguson, because he is in love with Catherine, but he bows out when Catherine and Frederic fall in love.

Frederic is ordered to the front for a period of several days, but while on the road, he orders the ambulance driver to turn back so he can express his love to Catherine, then promise that he will return to her.  Fearful that his friend is losing his head over a woman, Rinaldi has Catherine transferred to Milan.  Frederic, however, is wounded at the front, and Rinaldi makes a special trip to the front to operate on his "war brother," after which he relents and sends him to Milan to recuperate.

Frederic and Catherine's idyllic tryst in Milan, sanctioned by a priest who unofficially performs a wedding ceremony for them in Frederic's hospital room, comes to an end when a nurse discovers liquor bottles under Frederic's mattress and, observing that his days of recuperation are over, has him sent back to the front.  Catherine confides in her friend, Helen, that she is pregnant, and goes to Brissago, Switzerland to wait for Frederic.

Catherine and Frederic's letters to each other are returned thanks to Rinaldi's overzealous censorship, and Frederic, worried over her long silence, only confides his concern to his priest friend.  He then deserts and makes a perilous journey across Italy to find her.  When Ferguson tells him that Catherine is pregnant, but refuses to give him her location, Frederic takes out an advertisement asking Catherine to meet him at a hotel.

Rinaldi sees the advertisement and meets him, and tells him that the priest had told everyone he was dead.  Although Rinaldi offers to write a report that Frederic was only shell-shocked and did some heroic feat, Frederic refuses to return.  Finally recognizing the depth of Frederic's love for Catherine, Rinaldi informs him of her whereabouts, and Frederic immediately leaves with the help of the hotel owner, Harry, who lends him the use of his boat.

In Brissago, an ill and heartsick Catherine collapses after having all of her unopened letters to Frederic returned.  Frederic arrives in Brissago just as she is undergoing an emergency caesarean section.  The child is stillborn, and Catherine spends her final moments with Frederic, dying amid the jubilant noises of the armistice celebration.