Background: West Africa's Sahel is characterized by a dry and hot climate with limited rainfall that impairs the production of several crops. Sesame is a resilient crop that is well suited to this environment. Unfortunately, there is a lack of data relative to the status of its production in West Africa. We made investigations in four major sesame-growing areas of Senegal and Mali, into the status of the crop's production, its agronomic practices, the challenges farmers face and their preferences concerning the traits that should be improved. Results: A total of 256 sesame producers in 47 villages were interviewed using a semi-structured questionnaire. The results showed that sesame is a multi-ethnic crop and only 20% of the total fields owned by farmers were allocated to its cultivation. The yield and the seasonal production of sesame per farmer was quite weak showing that this crop is still a commodity grown on a small scale. Various cultivars were grown, and the most widely grown ones have considerable levels of oil (53–60.34%) and protein (18–21.89%) contents. In both countries, seed marketing was the main impediment the producers faced on account of a lack of reliable markets and of a considerable fluctuation in prices. Conclusions: Overall, the sesame sector is still traditional but is progressively developing and sesame could become an important cash crop for smallholders in West Africa's Sahel. Research programs should target the release of the varieties with higher yield, a stronger resistance to drought, heat, diseases and pests, a good seed quality and improved plant architecture. This study represents the first insight into the sesame sector in West Africa's Sahel, and our findings may guide researchers and policy-makers to boost this sector for ensuring food security and the improvement of small-scale farmers' livelihood.