The play opens in the powerful city state of Venice, famous as a center of trade and banking and for its military might. It is in the early hours of the morning, and two men — Roderigo, a young gentleman and former suitor of Senator Brabantio's daughter Desdemona, and Iago, an ensign who claims to have been passed over for promotion by Othello — are outside Senator Brabantio's house to tell him the news of his daughter's elopement with Othello, the Moor.
After sharing the news of the secret marriage in words calculated to alarm him, the treacherous and vindictive Iago quickly departs, leaving Roderigo to confirm the story. Feigning friendship and concern, Iago then meets with Othello and tells him of Brabantio's reaction. Brabantio, Othello, and Desdemona appear before the Duke of Venice. Although Brabantio accuses Othello of seducing his daughter by witchcraft, Othello explains that he won Desdemona by telling her his adventures, and Desdemona, called to testify, convinces the senators that she has freely gone with Othello and married him for love.
The Duke appoints Othello as general of the defense forces against the Turks, and he must leave for Cyprus immediately. Desdemona requests permission to accompany Othello to Cyprus. With the Duke's permission, Othello arranges for Desdemona to follow him later in another ship with Iago, whom he mistakenly believes is a trusted friend, and Iago's wife, Emilia. Iago convinces Roderigo that Desdemona will soon tire of Othello and that he should follow her to Cyprus. To himself, Iago decides to make use of Cassio, the man he deeply resents and who received the promotion he himself wanted, as the instrument to destroy Othello.
In Cyprus, Iago plots against Othello, planting the seed of doubt about Desdemona's fidelity and implicating Cassio as her lover. Using Roderigo, Iago arranges a fight that ultimately results in Cassio's demotion. Believing that his chances of reinstatement are better if he has Desdemona plead his case to her husband, Cassio, with Iago's help, arranges for a private meeting with Desdemona, who promises to speak on his behalf to Othello until his reconciliation with Othello is achieved.
As Cassio leaves, Iago and Othello appear. Othello notices Cassio's speedy departure, and Iago quickly seizes the opportunity to point out that Cassio seems to be trying to avoid the Moor. Desdemona immediately and enthusiastically begins to beg Othello to pardon Cassio, as she promised, and will not stop her pleading until Othello, preoccupied with other thoughts, agrees. The moment Desdemona and Emilia leave, however, Iago begins to plant seeds of doubt and suspicion in Othello's mind.
Othello, beset by uncertainty and anxiety, later demands of Iago some proof that Desdemona is unfaithful. Using a handkerchief that Desdemona later innocently drops, Iago convinces Othello that she has been unfaithful, and he stages a conversation with the innocent Cassio that further hardens the Moor's heart against his wife and her supposed lover. Convinced of his wife's betrayal and enraged and grieving, Othello rushes into action, making an agreement with Iago that he, Othello, will kill Desdemona, and Iago will dispose of Cassio.
Desdemona, true to her word to Cassio, continues to plead on his behalf, unknowingly confirming to Othello her unfaithfulness. He accuses her of falseness, and Desdemona, not knowing what she has done to offend, can only assure him that she loves him.
Meanwhile, the gullible Roderigo has abandoned all hope of Desdemona, but Iago urges him to kill Cassio and rekindle his hopes. Late that night, they attack Cassio in the street, but it is Cassio who wounds Roderigo. Iago rushes out and stabs Cassio in the leg. Othello, hearing Cassio's cries for help, believes that half of the revenge is completed and hastens to fulfil his undertaking.
Desdemona is in bed when Othello enters. He tells her to pray a last prayer as he has no wish to kill her soul. Realizing that he plans to murder her, Desdemona protests her innocence of any wrongdoing. Knowing that he doesn't believe her, she begs him to let her live just a little longer, but he smothers her with a pillow.
Emilia, Desdemona's servant and Iago's wife, upon discovering the ruse, raises the alarm and declares Iago a liar before Montano and Gratiano. She explains how Desdemona's handkerchief came into Cassio's possession, and when she refuses to be quiet, Iago stabs her. Cassio, wounded, confirms Emilia's story. A soldier to the last, Othello stands on his honor. Knowing that this is the end, he asks to be remembered as "one that loved not wisely but too well." Then he stabs himself and falls on the bed beside his wife, where he dies.