AISR was established at Brown University in 1993 through an anonymous gift of $5 million. Several months later, a $50-million gift – part of Ambassador Walter H. Annenberg's $500-million Challenge to the Nation to improve public education in America – enabled the fledgling Institute to considerably expand the scope of its work. In appreciation for the Ambassador's gift, AISR was renamed in his honor.

Under its first director, Dr. Theodore R. Sizer, founder and chairman of the Coalition of Essential Schools, AISR built upon the work of the Coalition but with a broader mission: to support sustained, focused efforts to enhance the quality of learning of children and youth across the country.

Following Dr. Sizer's retirement in 1996, a national search was undertaken for a new director. During the search period, Dr. Vartan Gregorian, who was then president of Brown University, served as acting director, and Ramón Cortines, a member of the Board of Overseers, as interim director.

In October 1998, Dr. Warren Simmons, then director of the Philadelphia Education Fund, was appointed executive director of AISR. Under Dr. Simmons’s leadership, the Institute adopted a mission statement that concentrated on the critical need to improve schooling in the nation’s urban communities.

In 2000, AISR opened a small office in New York City in conjunction with the launch of its Task Force on the Future of Urban Districts. In 2001, AISR moved its Providence operations to permanent headquarters on Benefit Street, just off the Brown campus.

The inaugural issue of AISR’s quarterly journal, Voices in Urban Education (VUE), was published in the spring of 2003.

AISR collaborated with the Education Department and other units within Brown University in 2005 to establish a Master’s Program in Urban Education Policy. In the summer of 2006, the first cohort of students entered the program.

In 2006, AISR's programs and staff were expanded with the assimilation of the Community Involvement Program, formerly affiliated with the Steinhardt School of Education at New York University. In 2007, AISR opened an expanded New York office in the Woolworth Building in lower Manhattan.

In 2012, AISR's Board of Overseers established a permanent, annual scholarship in honor of Ruth J. Simmons to be awarded to the Urban Education Policy graduate student who most epitomizes the former Brown University president’s commitment to educational equity and social justice. Simmons, who served as chair of AISR’s Board of Overseers since her installation as university president in 2001, urged the Institute and the university’s Education Department to collaborate on a graduate program in the study of urban public education.

In December 2015, Dr. Simmons stepped down as executive director of AISR, and  currently serves as senior fellow and continues to team-teach a course in urban systems and structure in Brown University’s Urban Education Policy master’s program. Former deputy director Michael Grady was named interim executive director. 

Susanna Loeb, an expert in education policy and a professor of education at Stanford University, has been appointed the next director of the Annenberg Institute, starting on July 1, 2018. Dr. Loeb's appointment reflects a refocusing of the Institute's mission, based on Brown University's strategic plan Building on Distinction.  

Note: While the Annenberg Institute for School Reform received an initial gift and other grants from the Annenberg Foundation (Ambassador Annenberg’s charitable trust), AISR is a separate entity from the Foundation and from other organizations that were beneficiaries of the Foundation and bear the Annenberg name.  AISR does not make grants and cannot consider proposals for funding from outside organizations.