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From his grave, the spirit of Henri Verdoux, who was an honest French bank clerk until the stock market crash of 1930, tells the story of how he began "liquidating" the opposite sex in order to support his wife and son.  In Paris, the quarrelsome Couvais family worries about their relative Vilma, who married a man named M. Varnay—one of Henri's aliases—after a two-week courtship, emptied her bank account and has not been heard from in three months.

Meanwhile, in a villa in the south of France, Henri, who has burned Vilma's body in his incinerator, receives her money in the mail and immediately telephones his stockbroker about investing it.  Calling himself M. Varnay, Henri then introduces himself to Marie Grosnay, a wealthy Parisian widow who is interested in buying the villa.  Henri frightens Marie with his abrupt, intense romantic overtures, and she leaves the house in a panic.

The Couvaises, meanwhile, go to the police about Vilma and learn that Detective Morrow suspects that a modern-day "Bluebeard" has murdered twelve missing women over the past three years.

Later, in Paris, Henri receives word from his stockbroker that he needs fifty thousand francs by the morning, so he visits one of his wives, Lydia Floray.  Henri tells the sour-faced Lydia that he has been building bridges in Indochina but was forced to return to France suddenly because of a growing financial crisis.  Insisting that the crisis will cause a run on the local banks, Henri convinces Lydia to withdraw all of her savings from the bank, and then kills her.

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The next day, Henri returns home to his wheelchair-bound first wife Mona, whom he loves, and their devoted son Peter.  In honor of their tenth wedding anniversary, Henri presents the unsuspecting Mona with the deed to their house and speaks lovingly about their marriage.

Claiming to have pressing business, Henri takes a train to Lyon the following day to see wife Annabella, an impressionable loudmouth who has won the lottery, and who believes he is a sea captain named Louis Bonheur.  After several unsuccessful attempts to kill Annabella, Henri ransacks her room to find her money and leaves again for Paris.  There, Henri arranges for flowers to be sent to Marie twice a week for a two-week period.  Later, during a visit with Mona, Henri learns about a lethal potion that causes a painless death and cannot be traced in an autopsy if used on a woman.

Back in Paris, Henri, posing as a furniture salesman, offers shelter to a beautiful Belgian refugee who has just been released from prison.  Henri plans to test his new poison on her, but when she talks about her love for her invalid veteran husband, who died while she was in jail, he is instead moved to help her and gives her money.  Then, Detective Morrow, who has been trailing Henri for weeks, arrests him for bigamy and fourteen murders, but Henri pours him the poisoned wine, killing him as he escorts his prisoner on a train.  Escaping unnoticed, Henri next tries to poison Annabella, but his potion is inadvertently switched with a peroxide bottle by the maid.

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Later, he attempts to drown Annabella in a lake, but once again fails.  In Paris, Henri finally convinces Marie to marry him, but when Annabella shows up unexpectedly at the wedding as someone's guest, Henri is forced to flee.  As Marie and the Couvais family prepare to have Henri arrested, the stock market crashes, and Henri loses all of the assets for which he murdered.  The Depression gives rise to a crisis in Europe and the rise of dictators.

Years later, Henri meets the Belgian woman, who has become wealthy through marriage to a munitions manufacturer, and tells her that he has lost all his money, his family, and his will to live.  While Henri dines with her at the top of the Eiffel Tower, he is recognized by the Couvaises and turns himself in.  Before he is sentenced at his trial, Henri states that the world, which is busy building mass weapons of destruction, encourages mass killing, making Henri an amateur by comparison.

Later, as he is about to be executed, Henri tells a reporter, "One murder makes a villain, millions a hero."  When a priest asks Henri to make his peace with God, he states that his problem is with man, then is led to the guillotine.