The present study provides a critical analysis of the introduction of exotic food crop species and their impact on agricultural transformations in Guinea-Bissau, based on survey data and a review of the literature from the 1800s to the present. It applies a multidisciplinary analysis to map historical and contemporary agrarian knowledge in Guinea-Bissau, presenting the first list of exotic cultivated species introduced in the country. Our results show that many introduced crops have gained widespread acceptance among local producers, with 63 exotic cultivated species native to America and Asia. The most representative families are Fabaceae, Solanaceae, and Anacardiaceae, including the country’s main former and current cash crops. First driven by peanuts in colonial times and by cashew after independence from 1980s onwards, Guinea-Bissau rapidly became one of Africa’s major exporters. The current cashew monoculture—like peanuts before it—relies almost exclusively on smallholder agriculture, raising concerns with regard to biodiversity, sustainability, and food security. The paper analyses historical trends in agro-economic transformations taking into account policies, programs, performance, and scientific research. Despite the existence of a long-standing single crop economy, further research is needed in this largely understudied country to assess the impact of long-term agrarian change.