She serves as the Bill & Melinda Gates Foundation's co-chair

Melinda started her charity endeavors in 1994 along with Bill, largely at the urging of Bill's father, William H. Gates, but also by following in the footsteps of Bill's mother, a devout philanthropist who had passed away earlier that year. The William H. Gates Foundation, their initial endeavor, pursued initiatives in the Pacific Northwest where they lived as well as global health initiatives. They established the Gates Learning Foundation in 1999 to support North American libraries, with a focus on bringing Internet technology to public libraries, three years after they first established the Gates Library Foundation. The Gates Millennium Scholars initiative, which funded minority study fellowships with $1 billion starting in 1999, came next.

In 2000, the pair established the Bill & Melinda Gates Foundation, which has an estimated endowment of $17 billion. The new business is headquartered in Seattle, Washington. The objectives of BMGF are to improve access to healthcare, lessen severe poverty worldwide, and increase chances for education and information technology. Melinda has won numerous prizes for her excellent work at the organization.

Melinda claims that her 1993 trip to Africa to view the wildlife gave her the idea to found the $50.7 billion organization. "It was incredible... But what touched us were the people, and the extreme poverty," explained Melinda during a TED Talk. "We started asking ourselves questions. Does it have to be like this?"

Melinda has since organized other multimillion-dollar grants, most recently providing Emory University with a $180 million grant to support infant mortality research.