Conventional and intensive agriculture systems represent an environmental challenge. This research aims at evaluating the economic and environmental implications of conventional and organic durum wheat production in Southern Italy by applying material flow analysis and the crop accounting method. The purpose is to evaluate and compare the natural resource consumption, waste generation and economic profitability of conventional and organic durum wheat farming, respectively. The functional unit is one hectare of cultivated land. System boundaries encompass all agronomic operations, from cradle to gate. The research applies a bottom-up approach and relies on either primary or secondary data. It emerges that organic durum wheat production reduces the use of synthetic chemical and phytosanitary products, as well as plastic waste, by up to 100%. Moreover, it decreases diesel use by 15%, with a consequent reduction in CO2 emissions, and also avoids soil and groundwater pollution. From an economic perspective, gross income for conventionally farmed durum wheat is still 55% higher compared to organic production. Public authorities should boost environmental sustainability by supporting organic production from either an economic or a social perspective, by enhancing the sharing of best practices, by certification for farmers’ groups, by research and innovation, and by incentives in taxation. Overall, this research represents a further step towards the adoption of sustainable agricultural practices.