In 1982 Reynolds was designated chancellor of the California State University system, replacing Glenn S. Dumke, who had held the job for twenty years, most of the life of the CSU system. During the late 1980s when the CSU system was contemplating a facility in the northern part of San Diego County, she was insistent that it be a full fledged university, California State University San Marcos, rather than a satellite campus of San Diego State University. It was the nation's first new state university in more than 20 years. Although her term was generally successful, she was forced to resign in 1990 when the system trustees questioned the substantial pay raises she had given herself, other top executives, and campus presidents. In addition, several trustees were displeased with a rule that she had put in place shortly before being forced to resign that required campus presidents who were 65 years of age or older to retire. Among those campus presidents forced to retire before this rule was rescinded were Jewel Plummer Cobb at California State University, Fullerton and Ellis E. McCune at Cal State Hayward. Ironically, the CSU Board of Trustees appointed McCune interim Chancellor while a search for Reynold's replacement was conducted.
When Reynolds became the chancellor of the City University of New York in 1990, the system's open enrollment policy had been the subject of debate for two decades. Reynolds defended open enrollment, and also worked to develop stronger college preparatory courses before students entered CUNY – which resulted in applicants with stronger academic records. Reynold's effort to introduce academic coordination among campuses and reduce duplicated programs was less successful, and provoked resistance from faculty and administrators. She angered mayor Rudolph W. Giuliani by attempting to relieve students on welfare from workfare requirements. She removed Leonard Jeffries as chairman of the black studies department at City College after he made anti-Semitic comments. In 1994 critics charged she spent too much time serving on the boards of five companies; Reynolds replied corporate contacts strengthened CUNY. According to The New York Times, when she left CUNY in 1997, she had a reputation as a "hard-charging, sometimes tyrannical administrator who can be utterly charming but also short-tempered and brusque."
In 1997 Reynolds was named president of the University of Alabama at Birmingham, where she established successful capital campaigns and new programs in arts, math and science to develop local teens into college-bound students. She continued to serve on several corporate boards, resulting in frequent absences from the university, a practice different from her predecessors and successors. In 2003, Reynolds claimed she was forced out of the presidency because of gender and age, and filed a federal discrimination complaint. She charged that system chancellor Thomas C. Meredith treated her "in a demeaning and sexist manner," including having her stand in line in the rain to buy theater tickets for him, restricting her contact with board members, and after firing her in 2002, offering her a retirement package less than those offered to other outgoing presidents. She accepted a one-year position as director of the university's Center for Community Outreach and Development from 2002 to 2003.
Books by W. Ann Reynolds
with Gary Parker and Rex Reynolds, DNA: The Key to Life
with Gary Parker, Mitosis and Meiosis
Beauty in the Bureaucracy, the David Dodds Henry lecture, 30 pp.