Abstract Human activities both aggravate and alleviate streamflow drought. Here we show that aggravation is dominant in contrasting cases around the world analysed with a consistent methodology. Our 28 cases included different combinations of human-water interactions. We found that water abstraction aggravated all drought characteristics, with increases of 20%–305% in total time in drought found across the case studies, and increases in total deficit of up to almost 3000%. Water transfers reduced drought time and deficit by up to 97%. In cases with both abstraction and water transfers into the catchment or augmenting streamflow from groundwater, the water inputs could not compensate for the aggravation of droughts due to abstraction and only shift the effects in space or time. Reservoir releases for downstream water use alleviated droughts in the dry season, but also led to deficits in the wet season by changing flow seasonality. This led to minor changes in average drought duration (−26 to +38%) and moderate changes in average drought deficit (−86 to +369%). Land use showed a smaller impact on streamflow drought, also with both increases and decreases observed (−48 to +98%). Sewage return flows and pipe leakage possibly counteracted the effects of increased imperviousness in urban areas; however, untangling the effects of land use change on streamflow drought is challenging. This synthesis of diverse global cases highlights the complexity of the human influence on streamflow drought and the added value of empirical comparative studies. Results indicate both intended and unintended consequences of water management and infrastructure on downstream society and ecosystems.