Caltech announced Chameau's decision in a letter Tuesday, with officials thanking him for his commitment to expanding resources for "high-risk, high-reward research."
In his resignation letter to the community, Chameau said there's historical significance to his new job as president of the King Abdullah University of Science and Technology.
With significant resources and a lofty mission, Chameau's new role will have him leading a school poised to "have a dramatic impact on the Kingdom of Saudi Arabia, the Middle East and the world," he said in a statement Tuesday.
Chameau was provost of the Georgia Institute of Technology before he became Caltech's eighth president in 2006—a role he believed would complete his career, leading to retirement in Pasadena, where Caltech is based.
While at Caltech, Chameau has supported the development of programs in areas of societal impact, including energy, information technology, medical science, and the environment, the school said in a statement.
Caltech is a private research university, known as the academic home of NASA's Jet Propulsion Laboratory and its highly selective admissions for top students. Caltech's faculty and alumni have won 32 Nobel Prizes.
Located on the Red Sea, the Saudi king's eponymous graduate research university enrolled its first students in 2009 and its first 10 Ph.D. students graduated in Dec. 2012.
In inaugural remarks, the absolute monarch said he'd dreamed of building it for more than 25 years and has pledged perpetual financial support, thanks in no small part to Saudi Arabia's considerable oil wealth.