The majority of that funding will be spent on helping you address challenges here in Africa," he said in an address at the African Union (AU) headquarters.
Mozambique's former First Lady Graça Machel welcomed his announcement, saying it came in a "moment of crisis".
"We are counting on Mr Gates' steadfast commitment to continue walking this path of transformation alongside us," she said.
Gates said his foundation, which has a long history of operating in Africa, would focus on improving primary healthcare.
Gates pointed to Rwanda as an example, saying it was already improving services using AI-enabled ultrasound to identify high-risk pregnancies.
Giving away 99% of his fortune could still leave the fifth-richest person in the world a billionaire, according to Bloomberg.
However, critics of his foundation say Gates uses its charitable status to avoid tax and that it has undue influence over the global health system. »