Understanding smoking patterns in the population is essential for formulating public health and tobacco control policies. Wastewater-based epidemiology (WBE) is a valuable complementary approach to conventional survey methods to measure tobacco use, providing non-invasive information in an objective and cost-effective manner. This study estimates tobacco use in an urban population at daily resolution and in a university town at weekly resolution in China. Wastewater samples were collected daily in an urban catchment (n = 279) and every week from a university town located within 13 km of the urban catchment (n = 43) in 2017–2018. The tobacco-related biomarkers, cotinine and hydroxycotinine, and nicotine were analyzed via direct injection liquid chromatography tandem mass spectrometry (LC-MS/MS). Per capita daily tobacco use was back-estimated based on cotinine in wastewater. Over the year of sampling, we observed an increasing trend in tobacco use in the urban catchment that corroborated with sales statistics in 2017–2018. Tobacco use in the urban area was estimated to be 1.16 cigarettes/person aged 15+/day, while it was estimated to be 0.60 cigarettes/person aged 15+/day in the university town. The level of tobacco use in the university town remained stable over the year in contrast to the urban area. The difference of tobacco use in the two catchments may be attributed to their demographic differences. Furthermore, the Tobacco-Free Campus Policy would be a possible reason for the lower level of tobacco use in the university town.