Returning from a victory, Macbeth is greeted by witches who hail him not only by his rightful title, Thane of Glamis, but also as Thane of Cawdor and future king. They hail his companion Banquo as the ancestor of a line of kings.
Messengers from the king greet Macbeth as Thane of Cawdor, explaining that the previous holder of the title has been executed. Macbeth broods over the other prophecy, but decides not to lift his hand against the king, while Banquo reflects that such prophecies could be a trap leading to destruction.
Lady Macbeth reads the letter in which Macbeth relates these events, and eagerly awaits his return, so that she can strengthen his resolve to obtain the crown. She greets with delight the news that King Duncan intends to pass the night at the castle, and when Macbeth arrives, easily convinces him to murder the king. Duncan appears with his retinue, including his son, Malcolm. On his way to commit the murder, Macbeth has a hallucination, seeing a dagger in the air, and strange noises accompany the deed. Stricken with terror and guilt, he is unable to take back the dagger which he has inadvertently brought with him. Lady Macbeth derides his fear, puts back the dagger and tells him to wash his hands and assume an appearance of innocence. Knocking at the gate heralds the arrival of Macduff and Banquo. Macduff goes to call the king while Banquo muses on the dreadful night, full of portents. Macduff's announcement of the murder provokes horror and cries to heaven for vengeance from all, including Macbeth and Lady Macbeth.
Macbeth confesses to his wife that he is brooding over the witches' prophecy that Banquo's descendants will be kings, and resolves to have him killed. Lady Macbeth exults that their claim to the throne will soon be unchallenged, even if at the cost of more killng. Banquo's forebodings are fulfilled when he is set upon and killed, but his son Fleance escapes.
A banquet is in progress and Lady Macbeth invites the guests to drink. One of the murderers reports that Banquo has been killed, but Fleance has escaped. Macbeth, about to take his seat, is confronted by Banquo's ghost, which only he can see. The guests are puzzled by his horror, but he recovers when the ghost vanishes and Lady Macbeth resumes her song in an attempt to restore the interrupted conviviality. But the ghost reappears and Macbeth's terror arouses the suspicions of the guests. Macduff decides to flee and Macbeth resolves to visit the witches again.
The witches prepare a brew. When Macbeth appears and demands to know his fate, they summon up spirits which tell him first to beware Macduff (whereupon he resolves to kill him), then that he cannot be killed by anyone born of woman (he decides to spare Macduff, but changes his mind again, wishing to be doubly sure) and that he cannot be killed until Birnam Wood comes to Dunsinane.
When he asks if Banquo's children will be kings, he is shown a vision of eight kings, the last holding a mirror showing still more, and Banquo indicating that they are his issue. Macbeth faints and the witches vanish. Lady Macbeth encourages him to kill Fleance and he tells her that he will also have Macduff and his family put to death. They swear vengeance on all who oppose them.
The refugees who have fled Macbeth's tyranny lament the unhappy state of their homeland and Macduff bewails the death of his family. Malcolm orders the soldiers to take branches from Birnam Wood as camouflage and exhorts them to follow him to free Scotland.
Lady Macbeth walks in her sleep, reliving the murders and trying to wash the blood from her hands. Faced with a stream of desertions, Macbeth takes comfort from the prophecies, though he is weary of life, and the news of his wife's death confirms his feelings about the futility of existence. When he learns that Birnam Wood is moving towards his castle, he realises that the witches have deceived him, but is determined to die fighting.
The scene changes to a plain where the battle rages. Macbeth learns that Macduff was not born naturally and is killed by him. Macduff hails Malcolm as king and the people join in thanksgiving.