A Wall Street Journal report on Friday alleged that the 76-year-old billionaire harassed massage therapists and forced one staff member to have sex with him.
Mr Wynn has denied wrongdoing, calling the stories "preposterous".
RNC chair Ronna McDaniel told US media she had accepted his resignation.
Mr Wynn has blamed his ex-wife, whom he is fighting in court, for the "slander".
"The instigation of these accusations is the continued work of my ex-wife Elaine Wynn, with whom I am involved in a terrible and nasty lawsuit," the billionaire said in a statement that his public relations team sent to the BBC on Friday.
What he is accused of
According to the Wall Street Journal, which said it had interviewed dozens of people who worked with Mr Wynn, he is accused of engaging in a pattern of abuse in which he often harassed massage therapists while alone in his private office.
The gambling industry giant paid $7.5m (£5.2m) to one manicurist who alleged she had been forced into sex by Mr Wynn, the paper claims citing court documents.
Why the US has so many sexual harassment cases in the US?
Female employees would fake appointments in order to avoid seeing him, or enlist others to pretend to be their assistants in order to avoid being alone with him.
Some would even hide in bathrooms or closets if they heard he was coming to their salon, the paper claimed.
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