On a trip to Venice in 1959, to celebrate completion of junior college, Annenberg met Seth Weingarten, who had just completed his undergraduate education at Princeton University and was looking forward to Yale Medical School. They quickly fell in love and, after only one year of studies at Columbia, Annenberg dropped out of school and married Weingarten at Inwood in 1960. They moved around the country, following her husband's career, and having four children in the process: Lauren, Roger, Gregory, and Charles. At her insistence, Weingarten accepted a position at UCLA and they established a permanent home in California. In 1975, she divorced Dr. Weingarten and in 1978 he won the custody of the children. One year later he offered Wallis full custody.
After she passed away in March 2009, Leonore Anneberg left the leadership of the Annenberg Foundation to Wallis and three of her children: Lauren, Gregory and Charles. Wallis Annenberg today carries on her father's legacy as a public benefactor. As Chairman and President of the Annenberg Foundation, she donates the family name and fortune to philanthropic and charitable projects, largely to the benefit of Los Angeles County. She is on the board of trustees at the Los Angeles County Museum of Art as well as at the Museum of Contemporary Art, Los Angeles. She is also a supporter of the Harlem Children's Zone, the Ojai Foundation's "Council project" for inner-city kids, and the Ocean Alliance. She serves on the Board of Trustees at the University of Southern California ; the Wallis Annenberg Hall at USC was opened at part of the Annenberg School in 2014. In 2017 she was honored with the USC University Medallion for her philanthropy and leadership. She is involved with the Wallis Annenberg Concourse at the Ronald Reagan UCLA Medical Center as well as the Wallis Annenberg Center for the Performing Arts, which held its opening gala in October 2013. She was inspired by and provided funding to build the Universally-Accessible Treehouse in Torrance, California. "It is thrilling to be able to make it possible for people of all ages and physical abilities to experience the world from a treehouse," said Wallis Annenberg. "There's a sense of vision, fun and pure escape that only such a structure can provide." Annenberg serves on the Board of Directors for the New York-based chapter of the foundation of Princess Charlene of Monaco. Her children Lauren Bon, Gregory Weingarten and Charles Weingarten serve on the board of directors of the Annenberg Foundation. Her son Roger Weingarten, a resident of Devereux in Santa Barbara, California who was diagnosed schizophrenic at age 15 like his namesake, is not on the board. Despite her father leaving the majority of his multibillion-dollar fortune to the Annenberg Foundation, it is estimated that Annenberg has a personal fortune in excess of five hundred million dollars.