Shakespeare sets up a contrast between the conventional Claudio and Hero, who have the usual expectations of each other, and Beatrice and Benedick, who are highly skeptical of romance and courtship and, seemingly, each other. Claudio is deceived by the jealous Don John into believing that Hero is prepared to abandon him for Claudio's friend and mentor, Don Pedro. This malicious fiction is soon dispelled, but Claudio seems not to have learned his lesson; he believes Don John a second time, and on a much more serious charge—that Hero is actually sleeping with other men, even on the night before her impending wedding to Claudio. Supported by Don Pedro, who also accepts the story (based on seeming visual evidence), Claudio publicly rejects Hero at the wedding ceremony. She is so shamed that her family is obliged to report that she is dead. Don John's plot is eventually unveiled by the bumbling constable Dogberry and his comically inept fellow constable, but not before the story of Hero has taken a nearly tragic turn. Claudio's slanders of Hero have so outraged her cousin Beatrice that she turns to Benedick, pleading with him to kill Claudio. Former friends are near the point of mayhem until the revelations of the night watch prove the villainy of Don John and the innocence of Hero.

Meanwhile, Beatrice and Benedick carry on “a kind of merry war” that tests their wits in clever but crushing repartees. Both have a reputation for being scornful and wary of marriage. Though attracted to each other for many reasons, they find it virtually impossible to get beyond the game of one-upping each other. Eventually their friends have to intervene with a virtuous ruse designed to trick each of them into believing that the other is hopelessly but secretly suffering the pangs of love. The ruse works because it is essentially true. At the play's end, both couples are united.

For a discussion of this play within the context of Shakespeare's entire corpus, see William Shakespeare: Shakespeare's plays and poems (Shakespeare, William).