The actor said the website published a "completely fabricated story" about his fiancé's mother opposing their upcoming nuptials for religious reasons.
Writing in the USA Today newspaper, Clooney said: "It says they joke about traditions in the Druze religion that end up with the death of the bride. Let me repeat that: the death of the bride.
"First of all, none of the story is factually true. Amal's mother is not Druze. She has not been to Beirut since Amal and I have been dating, and she is in no way against the marriage - but none of that is the issue.
"The irresponsibility, in this day and age, to exploit religious differences where none exist, is at the very least negligent and more appropriately dangerous.
"We have family members all over the world, and the idea that someone would inflame any part of that world for the sole reason of selling papers should be criminal."
The actor added that he would rarely respond to tabloid stories, but he felt compelled to in this instance because "it involves someone else and their safety or well-being."
The Ocean's 11 star added that he was used to stories being made up about him but this story involved "larger issues."
He continued: "When they put my family and my friends in harm's way, they cross far beyond just a laughable tabloid and into the arena of inciting violence."
The Daily Mail has since apologised to Clooney and promised a full investigation into a story.
In a statement they said: "The MailOnline story was not a fabrication but supplied in good faith by a reputable and trusted freelance journalist.
"We only became aware of Mr Clooney's concerns this morning and have launched a full investigation. However, we accept Mr Clooney's assurance that the story is inaccurate and we apologise to him, Miss Amal Alamuddin and her mother, Baria, for any distress caused."