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Our paper seeks to identify factors that inhibit and promote women’s success in seed businesses, through three case studies of women’s and men’s entrepreneurship across varying seed-related value chains and country contexts in Africa south of the Sahara. The cases include chicken seed dissemination in Ethiopia and Tanzania, tilapia seed production in Ghana, and marketing and trading of improved maize and sorghum seeds in Kenya. Applying a gender lens, we use qualitative methods to analyze women’s and men’s motivations to engage in seed businesses, the challenges they confront to start and succeed, and prospects for sustainability and continued success. We also use quantitative data to characterize the levels of empowerment of the entrepreneurs sampled. Results show that time flexibility and profitability of the business can be important considerations for women’s engagement in seed entrepreneurship, and the social normative context of the sector is also critical. Furthermore, outside support can be a key factor influencing women’s seed entrepreneurship, per the Kenya case.