Ten psychoactive substances (PSs) and metabolites were identified and quantified in 217 surface water samples collected across China to reveal the occurrence, distribution, and potential health risks in Chinese surface waters. The results showed the ubiquitous occurrence of caffeine (CFI), paraxanthine (PXT) and cotinine (CTN) at all the monitored sites, the concentrations of which ranged from not detected to 3460 ng L−1, while the remaining PSs were detected at trace levels (<50 ng L−1). High concentrations of diet-related PSs (CTN, CFI, and PXT) typically occurred in areas with high population densities. Traditional drugs tended to occur in megacities and the illegal manufacturing bases of the illicit drugs. Emerging drugs were found to be very popular across the whole country, with no significant differences among the samples. The risk assessment results suggest that drinking water containing these PS residues posed no potential human health risk in any life stage. However, the age-dependent risk quotients (RQs) of the 5 assessed PSs for the 12 age intervals ranged from < 1.0 × 10−7 to 0.005. In terms of the evaluated life stages, the RQs for early stages (from birth to <2 years) were significantly higher than the RQs for other stages.