A decade of research since the adoption of the Sustainable Development Goals (SDGs) argues that accurately measuring the relations between SDGs allows the identification of systemic leverage points that would unlock the achievement of the SDG agenda as a whole. While the literature on sustainable development linkages has evolved rapidly, regional variations tend to be overlooked. And yet, we have identified important differences between the SDG interlinkages in Africa and Sub-Saharan Africa in comparison to the World as a whole. The accurate identification of these links and regional differences between them hold important consequences for Africa achieving its development goals. We found that the observed significant interlinkages, more central SDGs, and nexuses between certain SDGs showed different patterns of variation between sub-Saharan Africa, Africa as a whole and the World. Leveraging significant interlinkages through policy, planning and practice can contribute to unlocking systemic advances to achieve the full SDG agenda. If regional differences in leverage points are not accurately identified, any policy and practice will be neither effective nor cost-efficient. Our findings also indicate that existing evidence on sustainable development that may be appropriate in the Global North may not be directly applicable in Africa, and therefore support contemporary calls for improving knowledge equity and evidence production between Global South and North.