Agricultural systems strongly impact ecosystems by driving terrestrial degradation, water depletion, and climate change. The Life Cycle Assessment allows for comprehensive analyses of the environmental impacts of food production. Nonetheless, its application still faces challenges due to cropping systems’ increased complexity and multifunctionality. Past research has emphasized the need for more holistic approaches to consider dynamic crop interactions and diverse functions of cropping systems, beyond just meeting the demand for foods and feeds. In this context, this study applied an alternative combined and multifunctional modelling approach to compare the environmental performances of two durum wheat cropping systems. The latter differed in crop rotation schedules, farming methods, tillage techniques, and genotypes grown (including both modern and old ones). Novel methodological choices were adopted in this study, aiming at best representing the complexity and peculiarities of these systems, by considering crop rotation effects and reflecting the main durum wheat stakeholders’ perspectives. The results showed that the organic low-input landrace-growing system (Case 1) had considerably lower environmental impacts than the conventional high-input one (Case 2), regardless of the functional unit. The environmental hotspots were the increased land occupation and the bare fallow for Case 1 and Case 2, respectively. At the endpoint level, the most affected impact categories for both the systems of analysis were land use, fine particulate matter formation, global warming (human health), and human non-carcinogenic toxicity. Also, the midpoint analysis pointed out important differences in terms of other assessed impact categories, with Case 1 better performing for the majority of them. The identified improvement solutions include the following: the enhancement of the yield performances and the optimization of nitrogen provision from the leguminous crop for Case1, the shift toward a more efficient rotational scheme, the reduction of the use of external inputs, and the avoidance of unnecessary soil tillage operations for Case 2.