After a rooftop chase in which a fellow policeman falls to his death, San Francisco detective John "Scottie" Ferguson retires out of fear of heights and vertigo. Midge, his ex-fiancée, says that another severe emotional shock may be the only cure.

Gavin Elster, an acquaintance from college, asks Scottie to follow his wife, Madeleine, claiming that she has been behaving strangely. Scottie follows Madeleine to the Mission San Francisco de Asís and the grave of Carlotta Valdes (1831–1857), and to the Legion of Honor art museum, where she gazes at the Portrait of Carlotta.

A local historian explains that Carlotta Valdes committed suicide: she had been the mistress of a wealthy married man and borne his child; the otherwise childless man kept the child and cast Carlotta aside. Carlotta (who Gavin fears is possessing Madeleine) is Madeleine's great-grandmother, although Madeleine has no knowledge of this and does not remember the places she visited. Scottie rescues her when she leaps into the bay at Fort Point.

The next day, Madeleine stops to deliver a letter of gratitude to Scottie, and they spend the day together. They travel to Muir Woods and Cypress Point on 17-Mile Drive, where they embrace. The next day, Madeleine recounts a nightmare. Scottie identifies its setting as Mission San Juan Bautista, the childhood home of Carlotta. He drives her there and they express their love for each other. Madeleine suddenly runs into the church and up the bell tower. Scottie, halted by his fear of heights, sees Madeleine plunge to her death.

An inquest declares her death to be a suicide. Gavin does not fault Scottie, but Scottie becomes clinically depressed and is sent to a sanatorium, almost catatonic. Following his release, he frequents the places Madeleine visited, often imagining that he sees her. One day, he notices a woman on the street who, although superficially very different, reminds him of Madeleine. She identifies herself as Judy Barton, from Salina, Kansas.

A flashback reveals that Judy was the person Scottie knew as "Madeleine Elster". She was impersonating Gavin's wife in an elaborate murder scheme. Gavin took advantage of Scottie's fear of heights to substitute his wife's freshly-killed body in the apparent "suicide jump". Judy considers confessing to Scottie but continues the charade because she loves him.

They begin seeing each other, but Scottie remains obsessed with "Madeleine". He asks Judy to change her clothes and dye her hair to resemble her. After she complies, he notices her wearing the necklace portrayed in Carlotta's painting. He realizes the truth and drives Judy back to the Mission.

There, he tells her he must re-enact the event that led to his madness, and admits he now knows that "Madeleine" and Judy are the same person and Judy was Gavin's mistress before being cast aside. He forces her up the bell tower and makes her admit her deceit. He reaches the top, finally conquering his fear of heights. Judy confesses that Gavin paid her to impersonate a "possessed" Madeleine. She begs Scottie to forgive her. He embraces Judy, but a shadowy figure — a nun investigating the noise — rises from the tower's trapdoor, startling her. Judy lunges backward and accidentally falls to her death. Scottie, bereaved once again but cured of his fear of heights, stands on the ledge while the nun rings the mission bell.