Engineered water systems such as wastewater treatment plants (WWTPs) are potential reservoirs of various biological risk factors (BRFs), including pathogens, antibiotic resistance genes (ARGs), and virulence factors (VFs). Currently, a BRF database relevant to engineered water systems on a global geographic scale is lacking. Here, we present the Global Wastewater Pathogen Database (GWPD), an online database that provides information on the diversity, abundance, and distribution of BRFs from 1302 metagenome samples obtained from 186 cities, 68 countries, and six continents. We sorted these samples into six types: sewer networks, influent, anoxic activated sludge, oxic activated sludge, effluent, and receiving/natural waters. In total, 476 pathogens, 442 ARGs, and 246 VFs were identified. As a multifunctional database, GWPD provides an interactive visualization of these BRFs in a world map, an information retrieval interface, and an online one-click service for BRF annotation from metagenome sequencing data. GWPD is built on a web service framework, which can be readily extended to future versions of GWPD by adding more functional modules and connecting to other data sources, such as epidemic databases, to support risk assessment and control in the context of “One Health.”