We conducted an in-depth exploration on the iteration and optimization of China-Africa university cooperation by tracing the evolution from “The 20+20 Cooperation Plan for Chinese and African Institutions of Higher Education” to the “China-Africa Universities 100 Cooperation Plan”. It is pointed out that the “The 20+20 Cooperation Plan for Chinese and African Institutions of Higher Education” actively explored diverse paths of China-Africa university cooperation，promoted the exchange of ideas and sharing of knowledge between China and Africa，drove China’s higher education towards an international transformation，and supported the inward-oriented development of African higher education. It emphasizes that the launch of the “China-Africa Universities 100 Cooperation Plan” not only marks the expansion of cooperation scale，but also symbolizes a systematic upgrade and iteration of the cooperation concept，model，quality，and effectiveness. We suggests that the China-Africa university cooperation represented by the “China-Africa Universities 100 Cooperation Plan” needs to make innovative efforts in optimizing its implementation strategies and paths. Firstly，to continuously strengthen and deepen cooperation in the field of STEM education；secondly，to fully recognize，explore，utilize and transform the structural advantage resources of African universities；thirdly，to focus on optimizing the diversified and multi-lateral cooperative relationships and building an ecological system of collaborative coexistence；fourthly，to improve the professional evaluation mechanism of the project and form a positive effect of collaborative development.