A ddPCR assay is presented to diagnose schistosomiasis japonica using feces, urine, saliva, and blood. The capability of the test to use noninvasive samples, its high sensitivity, and capacity to quantify infection intensity have public health implications for schistosomiasis control. Abstract Background Schistosomiasis japonica remains a major public health and socioeconomic concern in Southeast Asia. Sensitive and accurate diagnostics can play a pivotal role in achieving disease elimination goals. Methods We previously reported a novel droplet digital polymerase chain reaction (ddPCR) assay targeting the mitochondrial gene nad1 to diagnose schistosomiasis japonica. The tool identified both prepatent and patent infections using Schistosoma japonicum DNA isolated from serum, urine, salivary glands, and feces in a murine model. The assay was validated here using clinical samples collected from 412 subjects resident in an area moderately endemic for schistosomiasis in the Philippines. Results S. japonicum DNA present in human stool, serum, urine, and saliva was detected quantitatively with high sensitivity. The capability to diagnose cases of human schistosomiasis using noninvasively collected clinical samples, the higher level of sensitivity obtained compared with the microscopy-based Kato-Katz test, and the capacity to quantify infection intensity have important public health implications for schistosomiasis control and programs targeting other neglected tropical diseases. Conclusions This verified ddPCR method represents a valuable new tool for the diagnosis and surveillance of schistosomiasis, particularly in low-prevalence and low-intensity areas approaching elimination and in monitoring where disease emergence or re-emergence is a concern.