Monitoring antidepressant use is important for understanding mental health treatment status in populations and detecting potential misuse. Wastewater-based epidemiology (WBE) is a cost-effective approach to conduct such monitoring but requires valid correction factors (CFs) to accurately convert wastewater mass loads into consumption estimates. Most existing CFs are calculated from pharmacokinetic studies with small cohorts and are not specifically validated for WBE purposes. This study aimed to fill this knowledge gap by calibrating and validating the CFs for 5 commonly prescribed antidepressants. CFs were calibrated by dividing corresponding geo-located sales data by wastewater mass loads from 18 wastewater treatment plants in Australia for the same 3.5-year period. The refined CFs were 9.0 for fluoxetine, 6.4 for venlafaxine, and 25 for quetiapine. For the case of racemic citalopram and the pure S-enantiomer (escitalopram), individual CFs were proposed as 2.0 and 11, respectively. To validate their applicability, the new CFs were applied to independent datasets of wastewater samples collected in Belgium (2019 to 2022) and Australia (2020) and compared with sales data. The new calibrated CFs produced more accurate wastewater-based estimates of consumption for citalopram, escitalopram, fluoxetine, venlafaxine, and quetiapine, enhancing the capability of WBE in public health surveillance.