It is necessary to infuse a consistent supply of improved seed varieties into local sub-Saharan African crop production to improve low crop yields. The best distribution channel for the improved seed varieties may be small-scale commercial seed companies, but local entrepreneurs struggle to determine whether such businesses are viable. Using a multi-echelon supply chain approach, a decision support system (DSS) was designed to help African seed entrepreneurs make informed decisions about small-scale seed chain businesses. Specifically, entrepreneurs make decisions about where to locate seed enterprises, with which farmers to contract, and where to store seed. Optimization and simulation modeling are used to evaluate infrastructure variables such as distance, transportation cost, and storage loss and cost in three development level areas. Currently, the decision tool is used in Mozambique, Malawi, Kenya, and Tanzania. The model has supported the start-up of at least 17 small seed companies that are now introducing improved seed varieties into villages and farms. The DSS applies decision science research in a humanitarian application and offers important managerial implications about supply chain infrastructure to nongovernmental organizations and humanitarian groups. Such applications are vital as groups such as USAID, the Gates Foundation, and the International Crops Research Institute for the Semi-Arid Tropics (ICRISAT) continue to move toward micro-enterprise, value chain, and market-oriented development programs.