In a statement issued on Friday night, Star said Mr O'Neill would also step down from the board "with a departure date to be agreed".
"Mr O'Neill informed fellow directors late today of his decision," the company said.
"Interim arrangements will be announced once finalised. A search for a permanent CEO was commenced last month."
The NSW gaming regulator is investigating ASX-listed Star after media reports claiming the company enabled suspected money laundering, organised crime, fraud and foreign interference at its venues, including The Star Sydney.
Mr O'Neill was due to appear on Monday, but the hearing was pushed back one week until May 23.
Damning evidence at the inquiry has so far prompted the resignations of the gambling giant's chief executive Matt Bekier, chief financial officer Harry Theodore, chief casino officer Greg Hawkins, and chief legal and risk officer Paula Martin.
Many of Star's directors are also expected to step down after testimony of mismanagement, making way for renewal at the embattled company.
Directors Sally Pitkin and Gerard Bradley have already announced their intention to step down from the board.
Mr O'Neill, former boss of Australian Rugby Union, was appointed as the casino's interim executive chairman last month after Mr Bekier's resignation.
