Macbeth's most serious mistake was allowing his ambition to overcome his conscience. Macbeth despised the idea of killing King Duncan to gain the throne of Scotland. He knew such an act was abominable, but he ignored his conscience and his personal regard for Duncan. Instead, he chose to murder King Duncan while he slept--stabbing him to death in a horrible act of violence. Macbeth willingly gave up his own soul to gain political power.
After this first violation of moral behavior, Macbeth committed one crime after another, including the murder of Banquo and the destruction of Macduff's entire household. Macbeth accomplished each of these terrible deeds to maintain his power. He failed to realize that murder upon murder would make his countrymen despise him so thoroughly that they would rebel and join the English forces in overthrowing him.
Macbeth also made a serious mistake in underestimating the character of Malcolm, Duncan's son. Although he was young and inexperienced, Malcolm proved to be an effective leader who gained the help of the English in defeating Macbeth and regaining his place as rightful monarch in Scotland.
Finally, Macbeth's faith in the witches' prophecies clearly led to his undoing. It is only at the end of his life that he realizes how completely they had tricked him. Had he followed his own conscience, however, nothing the witches said could have hurt him. Their prophecies simply gave him a sense of security as he acted to fulfill his own selfish ambitions.