Agricultural production systems in semi-arid areas are vulnerable to a myriad of risks. Using a systems approach of risk framework and a mixed-methods research design, this paper sought to explore selected biophysical and socio-economic risks that contributed to vulnerability of agricultural production systems in the semi-arid lowlands of Mwanga District, Kilimanjaro Region, Tanzania. Despite the lack of statistically significant relationships between amounts of rainfall and crop production in the district, 30 focus group participants perceived that spatial and temporal changes of rainfall distribution as coupled with increased crop pest/disease outbreaks and soil loss contributed to vulnerability of agricultural production systems in terms of frequent crop failure and famine particularly amongst farmers who practised rain-fed farming in the semi-arid lowlands. Furthermore, participants perceived that crop production and yields were negatively influenced by poor marketing and institutional structures and that crop production and yields were negatively influenced by farmers' poor access to appropriate technologies including seeds, fertilizers, agrochemicals, agricultural machinery and infrastructure including modern irrigation schemes and all-weather roads. By way of conclusion, reduced vulnerability of agricultural production systems calls for integrated enhancement of farmers' capacity in addressing the biophysical, agro-industrial and institutional risks.