[6] Ayala's employment at UC Irvine ended in 2018 after the university issued a report relating to allegations of sexual harassment claims against him.

[14] Ayala served on the advisory board of the now defunct Campaign to Defend the Constitution, an organization that has lobbied in support of the separation of church and state.

He was also a critic of intelligent design theories, claiming that they are not only pseudoscience, but also misunderstood from a theological point of view.

Ayala debated Christian apologist William Lane Craig in November 2009 on the topic of intelligent design.

"[22] Four women (professor Kathleen Treseder, another professor, an assistant dean, and one graduate student),[23] alleged that Ayala had sexually harassed them, prompting an investigation led by Erik Pelowitz at UC Irvine's Office of Equal Opportunity and Diversity.

"[7] Ayala denied most allegations against him, and wrote to the university's chancellor, Howard Gillman, "I have never intentionally caused sexual harassment to anybody.

[7][23] Camilo José Cela Conde[23] and Elizabeth Loftus defended him, the latter saying that she was "shocked that this man's life was ruined over this collection of reactions to his behavior" and described the allegations as "thin.

[7] Ann Olivarius, a lawyer and sexual harassment expert who reviewed the report at the request of Science magazine, said that Ayala did not "have sex with students or pressure them directly for sex" but "clearly made multiple women feel degraded" and continued to do so "after senior university officials warned him to stop acting in these ways.

[24] The U.S. National Academy of Sciences rescinded Ayala's membership for violation of Section 4 of the NAS Code of Conduct, effective June 23, 2021.

[7][28][2] Ayala delivered a lecture at the Trotter Prize ceremony in 2011 entitled "Darwin's Gift to Science and Religion."

[32] Their marriage ended in divorce,[33] and in 1985 he married an ecologist named Hana Ayala (née Lostáková, born 1956).