Accurate modeling of in-sewer degradation of sewage-borne epidemiological biomarkers requires information on local wastewater temperature. We applied a deterministic, physical model to map theoretical wastewater temperature on a monthly scale worldwide and incorporated in the model estimated changes in the decay rate of 31 biomarkers of public health relevance frequently used in wastewater-based epidemiology (WBE). Over the course of a year, 75% of the world's global wastewater temperatures were estimated to fall into the temperature range of 6.9-34.4 °C. These non-fitted results obtained purely a priori were in good agreement with empirical observations (n = 400), as indicated by coefficients for Pearson (0.81; 0.76) and Spearman (0.86; 0.78) correlations for annual minima and maxima, respectively. Application of the Q10 rule for biochemical reaction rates showed that, depending on wastewater temperature, half-lives of sewage-borne biomarkers will change significantly (range: 27%-7,010%) from the baseline at ambient conditions (21 ± 1 °C; 100%). Importantly, these temperature-related modulations of in-sewer biomarker decay changed the size of the area observable by WBE; in the extreme, changes in the distal reach observable by WBE were predicted to be as large as 49-fold over the course of a year at a given location. This first model of spatial and temporal variability in wastewater temperature has multiple suggested applications, including (i) utility for explaining literature-reported discrepancies in the detectability and levels of sewage-borne biomarkers, (ii) identification of optimal and sub-optimal wastewater-borne biomarkers depending on their varying half-lives over the course of the year at the sampling location of interest, and (iii) estimating the effective size of the sewershed capture zone in WBE studies.