After completing his PhD, Zewail did postdoctoral research at the University of California, Berkeley, supervised by Charles B. Harris. Following this, he was awarded a faculty appointment at the California Institute of Technology in 1976, and eventually became the first Linus Pauling Chair in Chemical Physics there. He became a naturalized citizen of the United States on March 5, 1982. Zewail was the director of the Physical Biology Center for Ultrafast Science and Technology at the California Institute of Technology.
Zewail was nominated and participated in President Barack Obamas Presidential Council of Advisors on Science and Technology (PCAST), an advisory group of the nations leading scientists and engineers to advise the President and Vice President and formulate policy in the areas of science, technology, and innovation.