The resignation comes after scores were killed in a crackdown by security forces on loyalists of ousted Islamist president Mohamed Morsi.
"It has become too difficult to continue bearing responsibility for decisions I do not agree with and whose consequences I fear," ElBaradei said.
He said his conscience was troubled over the loss of life "particularly as I believe it could have been avoided".
"Unfortunately those who gain from what happened today are those who call for violence and terror, the extremist groups," he said.
Egypt on Wednesday declared a state of emergency after a security force crackdown on two huge Cairo protests by supporters of ousted president Mohamed Morsi turned into a bloodbath that left at least 124 people dead.
The violence in Cairo, that drew international condemnation, sparked deadly clashes across the country.
Morsi, Egypt's first freely elected president, was ousted by the military on July 3 with popular backing.
Deep political divisions in the country intensified following his removal.
Supporters of the Islamist leaders have vowed to keep fighting for his reinstatement at any cost.
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