This article discusses five of Africa’s most pressing development challenges for the 2020s, namely, infrastructure bottlenecks, fragility of economies due to underdiversification, youth unemployment, high fertility, and climate change. These either infringe on the region’s ability to grow or bring about volatility of growth, encumbering the continent’s efforts to develop. Policy will have to grapple with the challenges of How to diversify African economies to engender resilience, close the infrastructure gap, reign in fertility, generate productive employment opportunities for youth, and climate proof African agriculture. Governments will need to partner with, and leverage, the private sector to fast-track closing of these gaps. For instance, strong institutions and appropriate regulatory and policy frameworks should support capability building by enterprises and facilitate private sector participation in infrastructure. Bankability of projects is key if African governments are to leverage the “limitless” resources held by institutional investors to finance Africa’s infrastructure build. To secure long-term development, policy makers should decisively address fertility and youth employment challenges. Interventions that raise the opportunity cost of child bearing for women (ease access to education and paid work for women and girls) are effective in lowering fertility and should be pursued. Similarly, interventions that raise productivity in agriculture and household enterprises hold promise to absorb unemployed youth in the short to medium term, while reorienting education systems to science, technology, engineering, and math and vocational education, with emphasis on quality, should expand opportunities in the medium to long term. With respect to climate change mitigation and adaptation, policy should be directed at climate proofing agriculture and greening the electricity grid. Overcoming these challenges should expedite attainment of the 2030 sustainable development goals.