Soils are subjected to multiple anthropogenic modifications, but the synergistic impacts of simultaneous environmental stressors on below-ground communities are poorly understood. We used a large-scale (1152 plots), long-term (26 years), multi-factorial grassland experiment to assess the impact of five common agricultural practises (pesticides, herbicide, liming, fertilizers and grazing exclusion) and their interactive effects on the composition and activity of soil microbial communities. We confirmed that pH strongly impacts belowground communities, but further demonstrate that pH strongly mediates the impacts of other management factors. Notably, there was a significant interaction between liming and the effect of pesticide application, with only half of the taxa responding to pesticide being shared in both limed and unlimed treatments. Likewise, nutrient amendments significantly altered bacterial community structure in acidic soils. Not only do these results highlight an hierarchy of effect of commonly used agricultural practices but also the widespread interactions between treatments: many taxa were significantly affected by interactions between treatments, even in the absence of significant main effects. Furthermore, the results demonstrated that chemical amendments may not percolate deeply into physically unperturbed soils with effects concentrated between 0 and 30 cm, despite 20+ years of treatment. The research shows that future changes to agricultural practices will need to consider interactions among multiple factors.