As the global population becomes more concentrated in urban areas, resource consumption, including access to pharmaceuticals, is increasing and chemical use is also increasingly concentrated. Unfortunately, implementation of waste management systems and wastewater treatment infrastructure is not yet meeting these global megatrends. Herein, pharmaceuticals are indicators of an urbanizing water cycle; antidepressants are among the most commonly studied classes of these contaminants of emerging concern. In the present study, we performed a unique global hazard assessment of selective serotonin reuptake inhibitors (SSRIs) in water matrices across geographic regions and for common wastewater treatment technologies. SSRIs in the environment have primarily been reported from Europe (50%) followed by North America (38%) and Asia-Pacific (10%). Minimal to no monitoring data exists for many developing regions of the world, including Africa and South America. From probabilistic environmental exposure distributions, 5th and 95th percentiles for all SSRIs across all geographic regions were 2.31 and 3022.1 ng/L for influent, 5.3 and 841.6 ng/L for effluent, 0.8 and 127.7 ng/L for freshwater, and 0.5 and 22.3 ng/L for coastal and marine systems, respectively. To estimate the potential hazards of SSRIs in the aquatic environment, percent exceedances of therapeutic hazard values of specific SSRIs, without recommended safety factors, were identified within and among geographic regions. For influent sewage and wastewater effluents, sertraline exceedances were observed 49% and 29% of the time, respectively, demonstrating the need to better understand emerging water quality hazards of SSRIs in urban freshwater and coastal ecosystems. This unique global review and analysis identified regions where more monitoring is necessary, and compounds requiring toxicological attention, particularly with increasing aquatic reports of behavioral perturbations elicited by SSRIs.