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Iceberg calving accounts for between 30–60 % of net mass loss from the Greenland Ice Sheet, which has intensified and is now the single largest contributor to global sea level rise in the cryosphere. Changes to calving rates and the dynamics of calving glaciers represent one of the largest uncertainties in projections of future sea level rise. A growing body of observational evidence suggests that calving glaciers respond rapidly to regional environmental change, but predictive capacity is limited by the lack of suitable models capable of simulating the calving mechanism realistically. Here, we use a 3D full-Stokes calving model to investigate the environmental sensitivity of Store Glacier, a large outlet glacier in West Greenland. We focus on two environmental processes: undercutting by submarine melting and buttressing by ice mélange, and our results indicate that Store Glacier is likely to be able to withstand moderate warming perturbations in which the former is increased by 50 % and the latter reduced equivalently. However, severe perturbation with a doubling of submarine melt rates or a complete loss of ice mélange destabilizes the calving front in our model runs. Furthermore, our analysis reveals that stress and fracture patterns at Store’s terminus are complex and varied, primarily due to the influence of basal topography. Calving style and environmental sensitivity varies greatly, with propagation of surface crevasses significantly influencing iceberg production in the northern side, whereas basal crevasses dominate in the south. Any future retreat is likely to be initiated in the southern side by a combination of increased melt rate in summer and reduced mélange strength in winter. The lateral variability, as well as the importance of rotational and bending forces at the terminus, underlines the importance of using the 3D full-Stokes stress solution when modelling Greenland’s calving glaciers.