The play takes place in Scotland. Duncan, the king of Scotland, is at war with the king of Norway. As the play opens, he learns of Macbeth's bravery in a victorious battle against Macdonald—a Scot who sided with the Norwegians. At the same time, news arrives concerning the arrest of the treacherous Thane of Cawdor. Duncan decides to give the title of Thane of Cawdor to Macbeth.
As Macbeth and Banquo return home from battle, they meet three witches. The witches predict that Macbeth will be thane of Cawdor and king of Scotland, and that Banquo will be the father of kings. After the witches disappear, Macbeth and Banquo meet two noblemen Ross and Angus, who announce Macbeth's new title as thane of Cawdor. Upon hearing this, Macbeth begins to contemplate the murder of Duncan in order to realize the witches' second prophecy.
Macbeth and Banquo meet with Duncan, who announces that he is going to pay Macbeth a visit at his castle. Macbeth rides ahead to prepare his household. Meanwhile, Lady Macbeth receives a letter from Macbeth informing her of the witches' prophesy and its subsequent realization. A servant appears to inform her of Duncan's approach. Energized by the news, Lady Macbeth invokes supernatural powers to strip her of feminine softness and thus prepare her for the murder of Duncan. When Macbeth arrives, Lady Macbeth tells him that she will plot Duncan's murder.
When Duncan arrives at the castle, Lady Macbeth greets him alone. When Macbeth fails to appear, Lady Macbeth finds him is in his room, contemplating the weighty and evil decision to kill Duncan. Lady Macbeth taunts him by telling him that he will only be a man if he kills Duncan. She then tells him her plan for the murder, which Macbeth accepts: they will kill him while his drunken bodyguards sleep, then plant incriminating evidence on the bodyguards.
Macbeth sees a vision of a bloody dagger floating before him, leading him to Duncan's room. When he hears Lady Macbeth ring the bell to signal the completion of her preparations, Macbeth sets out to complete his part in the murderous plan.
Lady Macbeth waits for Macbeth to finish the act of regicide. Macbeth enters, still carrying the bloody daggers. Lady Macbeth again chastises him for his weak-mindedness and plants the daggers on the bodyguards herself. While she does so, Macbeth imagines that he hears a haunting voice saying that he shall sleep no more. Lady Macbeth returns and assures Macbeth that "a little water clears us of this deed" (II ii 65).
As the thanes Macduff and Lennox arrive, the porter pretends that he is guarding the gate to hell. Immediately thereafter, Macduff discovers Duncan’s dead body. Macbeth kills the two bodyguards, claiming that he was overcome with a fit of grief and rage when he saw them with the bloody daggers. Duncan's sons Malcolm and Donalbain, fearing their lives to be in danger, flee to England and Ireland. Their flight brings them under suspicion of conspiring against Duncan. Macbeth is thus crowned king of Scotland.
In an attempt to thwart the witches' prophesy that Banquo will father kings, Macbeth hires two murderers to kill Banquo and his son Fleance. Lady Macbeth is left uninformed of these plans. A third murderer joins the other two on the heath and the three men kill Banquo. Fleance, however, manages to escape.
Banquo’s ghost appears to Macbeth as he sits down to a celebratory banquet, sending him into a frenzy of terror. Lady Macbeth attempts to cover up for his odd behavior but the banquet comes to a premature end as the thanes begin to question Macbeth's sanity. Macbeth decides that he must revisit the witches to look into the future once more.
Meanwhile, Macbeth's thanes begin to turn against him. Macduff meets Malcolm in England to prepare an army to march on Scotland.
The witches show Macbeth three apparitions. The first warns him against Macduff, the second tells him to fear no man born of woman, and the third prophesizes that he will fall only when Birnam Wood comes to Dunsinane castle. Macbeth takes this as a prophecy that he is infallible. When he asks the witches if their prophesy about Banquo will come true, they show him a procession of eight kings, all of whom look like Banquo.
Meanwhile in England, Malcolm tests Macduff's loyalty by pretending to confess to multiple sins and malicious ambitions. When Macduff proves his loyalty to Scotland, the two strategize for their offensive against Macbeth. Back in Scotland, Macbeth has Macduff’s wife and children murdered.
Lady Macbeth suffers from bouts of sleepwalking. To a doctor who observes her symptoms, she unwittingly reveals her guilt as she pronounces that she cannot wash her hands clean of bloodstains. Macbeth is too preoccupied with battle preparations to pay much heed to her dreams and expresses anger when the doctor says he cannot cure her. Just as the English army led by Malcolm, Macduff, Siward approaches, Lady Macbeth’s cry of death is heard in the castle. When Macbeth hears of her death, he comments that she should have died at a future date and muses on the meaninglessness of life.
Taking the witches’ second prophecies in good faith, Macbeth still believes that he is impregnable to the approaching army. But Malcolm has instructed each man in the English army to cut a tree branch from Birnam Wood and hold it up to disguise the army’s total numbers. As a result, Macbeth's servant reports that he has seen a seemingly impossible sight: Birnam Wood seems to be moving toward the castle. Macbeth is shaken but still engages the oncoming army.
In battle, Macbeth kills Young Siward, the English general's brave son. Macduff then challenges Macbeth. As they fight, Macduff reveals that he was not "of woman born" but was "untimely ripped" from his mother's womb (V x 13-16). Macbeth is stunned but refuses to yield to Macduff. Macduff kills him and decapitates him. At the end of the play, Malcolm is proclaimed the new king of Scotland.