This study investigated the occurrence and concentration of emerging and persistent contaminants (EPC) within a variety of land uses in the Ping River catchment of northern Thailand. Urban sites exhibited the highest levels of contamination, followed by agriculture and rural sites. The high presence of pharmaceuticals, daily use compounds, and industrial-related compounds in urban areas indicates significant contributions of wastewater likely associated with drainage from areas with manufacturing, repair, and medical activities, as well as dense residential living. The ubiquitous occurrence of daily use compounds (caffeine and acesulfame) in all land-use types was an indicator of significant gray water pollution in the catchment. Seasonal variations in EPC occurrence were not significant, possibly due to constant mixing or flushing of EPCs within the large catchment through multiple flow pathways. The complexity of EPC occurrence in the mixed-use catchment was dependent on factors related to EPC usage and processes, both natural and anthropogenic, that affect EPC entry into the environment from a variety of sources and then flow to the river system and, potentially, the groundwater. The findings highlight the heterogeneity and dynamic nature of mixed-use anthropogenic landscapes and emphasize the need for further research on the influence of hydrological connectivity on the EPC presence and intensity in such settings.