Ms Hook has confirmed she will not be renewing her four year contract when it expires in early 2027 and has opted to "pass the baton" to a new Olympic leader.
She is leaving as Games organisers move to the critical phase of operations, project and event delivery.
Ms Hook said the time was right to step away to ensure a smooth transition, backing Brisbane 2032 to deliver a Games that would make every Australian proud.
"During the past four years, I have achieved everything we had hoped for and had many amazing experiences along the way," she said in a statement.
"The foundations for success have been well laid. This is the right time to hand over to a new CEO for the next phase. Â
"I look forward to seeing the Games Vision brought to life and you can be sure I will be the greatest fan in the stands at the 2032 Games."
A new CEO is expected to be announced in the coming months, with Games organisers on Tuesday confirming a global executive search would "commence immediately".
"Cindy has been an exceptional leader whose passion, drive and strategic intellect has set Brisbane 2032 up for success for our years ahead," Brisbane 2032 president Andrew Liveris said.
"Cindy commenced when the Organising Committee was a fledgling startup and has transformed Brisbane 2032 into a thriving organisation ready to go to the next level of Games execution."
Highlights from Ms Hook's stint included working with government partners on a legacy strategy, defining the Games Vision, securing the first commercial partner and unveiling the Games emblem.
The woman who will oversee the Brisbane Games' delivery, Mikaela Cojuangco Jaworski, said Ms Hook had built the 2032 organising committee "from the ground up".
"Cindy has helped turn opportunity into concrete progress, leaving the organisation ready for its next chapter," the 2032 Olympics co-ordination commission chair said.
Australian Olympic Committee president Ian Chesterman thanked Ms Hook, saying she not only helped establish the organising committee but also built its international reputation.
"She has understood the importance of delivering not only a successful Games, but also a lasting legacy for the Olympic movement in Australia," he said.
"She has shared our commitment to putting athletes and their experience at the heart of the Games.
"Her leadership has laid strong foundations for the successful delivery of the Games in 2032."
United States executive Ms Hook was Deloitte Asia Pacific CEO in Singapore before taking the Brisbane role when she was appointed in December 2022.
7°C