Environmental perturbation, climate change and international commerce are important drivers for biological invasions. Climate anomalies can further increase levels of habitat disturbance and act synergistically to elevate invasion risk. Herein, we use a historical data set from the upper San Francisco Estuary to provide the first empirical evidence for facilitation of invasions by climate extremes. Invasive zooplankton species did not become established in this estuary until the 1970s when increasing propagule pressure from Asia coincided with extended drought periods. Hydrological management exacerbated the effects of post-1960 droughts and reduced freshwater inflow even further, increasing drought severity and allowing unusually extreme salinity intrusions. Native zooplankton experienced unprecedented conditions of high salinity and intensified benthic grazing, and life history attributes of invasive zooplankton were advantageous enough during droughts to outcompete native species and colonise the system. Extreme climatic events can therefore act synergistically with environmental perturbation to facilitate the establishment of invasive species.