This paper creates and applies a computational model of irrigation agriculture in order to study the effects of salinization in Mesopotamia, with the model developed applicable to cases beyond that studied here. Scholars have long suspected that central and southern Mesopotamia present environments which limited agricultural production over the long-term. In regions such as central Mesopotamia, where salinization likely affected settlement and agriculture in different periods but was more manageable than in more southern regions, fallowing regimes, natural and engineered leaching, and decisions made on when to crop were strategies applied in order to limit the effects of salinization. In this paper, we assess the effectiveness of these coping strategies by incorporating projected climate, soil, and landscape conditions with agricultural practices. The simulation results not only demonstrate the effectiveness and limitations of inhibiting progressive salinization, but they can be compared with the archaeological record in order to determine if the results could reasonably be matched with past events and help to interpret settlement history.