The 76-year-old former business rival turned political ally of President Donald Trump had assumed the RNC position after Trump took office in January 2017.
Wynn has denied the allegations, first published in The Wall Street Journal on Friday, and accused his ex-wife Elaine of instigating the accusations as part of a "terrible and nasty lawsuit" seeking a revised divorce settlement.
"Today, I accepted Steve Wynn's resignation as Republican National Committee finance chair," RNC chair Ronna Romney McDaniel said in a statement to US media on Saturday.
A towering figure in the gambling world, Wynn has been a prolific Republican donor whose empire includes casinos in Macau.
The allegations include a married manicurist who said Wynn forced her to have sex shortly after he opened his flagship Wynn Las Vegas in 2005, and whom he later paid a $7.5 million settlement, the Journal reported.
"The idea that I ever assaulted any woman is preposterous," Wynn said in a statement.
"We find ourselves in a world where people can make allegations, regardless of the truth, and a person is left with the choice of weathering insulting publicity or engaging in multi-year lawsuits."
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.
It was the first time that the US sexual harassment watershed has centred on the CEO and founder of a major publicly held company -- whose shares tumbled 7.8 per cent following the report's publication.
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