Dr. Ayala has been a member of the President's Committee of Advisors on Science and Technology (1994-2001) and president and chairman of the Board of the American Association for the Advancement of Science. He has been elected president of Sigma Xi (2003-06), the Scientific Research Society of the U.S. In 2003, he was appointed University Professor, the highest title at the University of California.

He was a National Medal of Science laureate for 2001. Other honors include elected membership in the National Academy of Sciences, the American Academy of Arts and Sciences, and the American Philosophical Society. He is a fellow of the American Association for the Advancement of Science and the California Academy of Sciences. He received the Gold Honorary Gregor Mendel Medal from the Czech Academy of Sciences, the Gold Medal of the Accademia Nazionale dei Lincei, the Gold Medal of the Stazione Zoologica of Naples, the President's Award of the American Institute of Biological Sciences, the Scientific Freedom and Responsibility Award and the 150th Anniversary Leadership Medal from the AAAS, the Medal of the College of France, the UC Irvine Medal, the 1998 Distinguished Scientist Award from SACNAS, and the William Procter Prize for Scientific Achievement from Sigma Xi in 2000. His research focuses on population and evolutionary genetics, including the genetic diversity of populations, the origin of malaria, the population structure of parasitic protozoa, and the molecular clock of evolution.