Layne, who was with the company for nine years, will also step down from the board of directors, according to a Howard Hughes Corp. news release.
Company officials said they valued Layne's leadership during the pandemic this year.
"Paul's superb oversight of the development of The Woodlands and his strong stewardship during the pandemic have created and preserved tremendous value for our shareholders, positioning Howard Hughes for long-term success," said Bill Ackman, the chair of The Howard Hughes Corp board.
O'Reilly had been CFO at the company since 2016 and was appointed president in June, according to a news release. The company's board of directors will conduct a search for a permanent CEO.
"It has been an exceptionally fulfilling privilege to lead The Howard Hughes Corporation through such a critical period in the company's history," Layne said in a statement. "Together, we have come through stronger than ever, and I am incredibly proud of all we have achieved."