The paper provides a speculative reflection on the power of modern science, technology and innovation systems (STI) for revealing some distinctive style of modernity in Africa. The modernization of these systems, as the backbones of any mode of modernity, also requires the modernization of our mental or intellectual costumes. This process is essentially the passage from closed, self-confirming, faith-based, customary, totalizing or terrorizing knowledge systems to essentially falsifiable, evidence-based, scientifically-established and technically-proven innovative knowledge systems. In these systems scientific knowledge can be construed as a theory of the real and as a technology of truth and understood as the epistemological foundation of any form of Afro-modernity. It is also the passage from the ‘Book of Scripture’ to the ‘Book of Nature’ or from the submission to the white man’s colonizing gods to the more authentic and genuine African identities, beliefs and values, such as those embodied in the concept ofubuntu. In this perspective rejuvenating knowledge systems can purge Abrahamic and Shamanic worldviews of non-scientific constituents and open a path from the mostly totemic, enchanted, mystified, supernatural, patriarchal / phallocratic and over-religious worldviews and mindsets of pre-modern Africa to the more desacralized, secular, rational, liberal, enlightened and autonomous worldviews and mindsets of modernity. This paradigmatic shift toward modern ways of knowing and understanding requires championing the scientific method, the rule of technique and innovation as well as promoting decisive scientific arbitrations, increased technical mediations and a redefinition of STI’s relationships with religious, cultural, social and economic life. For this shift to occur there is a need to better appreciate modern science as a method of both calculative and subversive thinking, as a means of achieving the systematic renovation of conventional / medieval / pre-modern realities and as a way to reconstruct and re-order African realities from fresh fundamentals and from the latest scientific insights. This may require strengthening various capacities to probe, undermine and rationalize oppressive systems (religious, cultural, social, economic, political). It may also require re-cosmologizing, re-mythologizing, ‘re-prophetizing’, re-charlatanizing and re-directing the evolution of the African reality toward a region free of wishful thinking, fallacies, lies, superstitions, prejudices, magic and witchcraft and toward an Islam-free and Christian-free scientifically-informed free-thinking innovative post-colony. The necessary capacities for achieving this shift toward more innovative scientific and technical orders and systems are grouped into eight areas.