"In the last couple of weeks, I have found myself the focus of an avalanche of negative publicity," Wynn said in a statement.
"As I have reflected upon the environment this has created -- one in which a rush to judgment takes precedence over everything else, including the facts -- I have reached the conclusion I cannot continue to be effective in my current roles."
The 76-year-old former business rival turned political ally of President Donald Trump resigned late last month from his role as Republican National Committee finance chairman, a post he had assumed after Trump took office in January 2017.
Wynn has denied the allegations, first published in The Wall Street Journal, and accused his ex-wife Elaine of instigating the accusations as part of a "terrible and nasty lawsuit" seeking a revised divorce settlement.
A towering figure in the gambling world, Wynn has been a prolific Republican donor whose empire includes casinos in Macau.
"Steve Wynn is an industry giant," said the company's non-executive director of the board Boone Wayson, adding that it was with a "collective heavy heart" that the board accepted Wynn's resignation.
"He is a philanthropist and a beloved leader and visionary. He played the pivotal role in transforming Las Vegas into the entertainment destination it is today."
Former employees said their awareness of Wynn's power, combined with the knowledge that they had some of the best-paying jobs in Las Vegas added up to a feeling of dependence and intimidation when he made requests, the Journal reported.
One former massage therapist said he instructed her to manually stimulate his genitalia during sessions, and that she felt she had to agree because he was her boss.
Another former worker said Wynn rubbed his genitals and commented about what he would like to do with her sexually, and once grabbed her waist and told her to kiss him.
Wynn Resorts, which employs 23,000 people around the world, also lashed out at Elaine Wynn and said not one complaint had been made about Wynn on a company hotline.
The Journal contacted more than 150 people who work or had worked for Wynn in its reporting.
It was the first time that the US sexual harassment watershed has centered on the CEO and founder of a major publicly held company.
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