In their annual letter released today, the couple laid out their upbeat vision for a technology-driven wave of change that will lift hundreds of millions out of poverty by 2030.
"Our big bet is that in the next 15 years, the lives of the poor are going to improve more than at any time in the history of the world," Melinda Gates told AFP in an interview.
Child deaths are predicted to be cut by half, polio will be wiped out while the fight against malaria, a major killer in Africa, will make strides with vaccines and a single-dose cure.
Africa can achieve food security by 2030 with access to innovation in agriculture to help farmers, the Gates said in their letter, a vision statement that has been released annually since 2009.
"Seven out of 10 adults in Africa are farmers. When they get new seeds that are drought-resistant and as the climate changes, they can still get more yield off their farms," said Melinda.
"It means they can feed their families and put the crops on the market." Mobile banking has been popularised in Kenya, but the Gates Foundation is working to bring the financial tool to the poor in Tanzania, India, Bangladesh, the Philippines and Uganda.
She sees potential for poverty reduction through online education and the development of software, especially for cell phones to help teachers and students.
The Gates' "big bet" that the world will be a better place in 2030 comes at a time of gloom in international circles with humanitarian agencies struggling to help a record number of people displaced by conflicts.
The letter acknowledges that there are skeptics and that "we shouldn't lose sight of the fact that a handful of the worst-off countries will continue to struggle".