Responses to future changes in climatic and socio-economic conditions can be expected to vary between sectors and regions, reflecting differential sensitivity to these highly uncertain factors. A sensitivity analysis was conducted using a suite of impact models (for health, agriculture, biodiversity, land use, floods and forestry) across Europe with respect to changes in key climate and socio-economic variables. Depending on the indicators, aggregated grid or indicative site results are reported for eight rectangular sub-regions that together span Europe from northern Finland to southern Spain and from western Ireland to the Baltic States and eastern Mediterranean, each plotted as scenario-neutral impact response surfaces (IRSs). These depict the modelled behaviour of an impact variable in response to changes in two key explanatory variables. To our knowledge, this is the first time the IRS approach has been applied to changes in socio-economic drivers and over such large regions. The British Isles region showed the smallest sensitivity to both temperature and precipitation, whereas Central Europe showed the strongest responses to temperature and Eastern Europe to precipitation. Across the regions, sensitivity to temperature was lowest for the two indicators of river discharge and highest for Norway spruce productivity. Sensitivity to precipitation was lowest for intensive agricultural land use, maize and potato yields and Scots pine productivity, and highest for Norway spruce productivity. Under future climate projections, North-eastern Europe showed increases in yields of all crops and productivity of all tree species, whereas Central and East Europe showed declines. River discharge indicators and forest productivity (except Holm oak) were projected to decline over southern European regions. Responses were more sensitive to socio-economic than to climate drivers for some impact indicators, as demonstrated for heat-related mortality, coastal flooding and land use.