Hydrological processes determine the transport of nutrients and passage of diffuse pollution. Consequently, catchments are likely to exhibit individual hydrochemical responses (sensitivities) to climate change, which are expected to alter the timing and amount of runoff, and to impact in-stream water quality. In developing robust catchment management strategies and quantifying plausible future hydrochemical conditions it is therefore equally important to consider the potential for spatial variability in, and causal factors of, catchment sensitivity, as it is to explore future changes in climatic pressures. This study seeks to identify those factors which influence hydrochemical sensitivity to climate change. A perturbed physics ensemble (PPE), derived from a series of global climate model (GCM) variants with specific climate sensitivities was used to project future climate change and uncertainty. Using the INtegrated CAtchment model of Phosphorus dynamics (INCA-P), we quantified potential hydrochemical responses in four neighbouring catchments (with similar land use but varying topographic and geological characteristics) in southern Ontario, Canada. Responses were assessed by comparing a 30 year baseline (1968–1997) to two future periods: 2020–2049 and 2060–2089. Although projected climate change and uncertainties were similar across these catchments, hydrochemical responses (sensitivities) were highly varied. Sensitivity was governed by quaternary geology (influencing flow pathways) and nutrient transport mechanisms. Clay-rich catchments were most sensitive, with total phosphorus (TP) being rapidly transported to rivers via overland flow. In these catchments large annual reductions in TP loads were projected. Sensitivity in the other two catchments, dominated by sandy loams, was lower due to a larger proportion of soil matrix flow, longer soil water residence times and seasonal variability in soil-P saturation. Here smaller changes in TP loads, predominantly increases, were projected. These results suggest that the clay content of soils could be a good indicator of the sensitivity of catchments to climatic input, and reinforces calls for catchment-specific management plans.