Estimation of community-wide consumption of illicit drugs through wastewater analysis is a new concept in Africa although widely applied in developed nations as wastewater-based epidemiology (WBE). It is an important tool that can be used in understanding supply and demand patterns of illicit drug use on a local, national, and international scale. Information on illicit drug use is currently limited in Africa, because of a lack of monitoring structures by governments and financial constraints. This study hopes to bridge that gap by contributing to Africa's baseline information on illicit drug use. This study provides the first application of wastewater analysis to quantitatively evaluate daily illicit drug use in the eThekwini Metropolitan Municipality of KwaZulu-Natal Province of South Africa by quantifying the major urinary excreted metabolites, called drug target residues (DTRs), in raw wastewater from four major wastewater treatment plants (WWTPs) sampled for a week. The results showed that cocaine was the dominant illicit drug consumed in the catchment followed by amphetamine, methamphetamine, 3,4-methylenedioxymethamphetamine and 3,4-methylenedioxyamphetamine, with a per capita use of 360–3000 mg day−1 1000 inh−1, 47–800 mg day−1 1000 inh−1, 19–120 mg day −1 1000 inh−1, not detected (ND) to 4.9 mg day−1 1000 inh−1, and ND to 410 g day−1 1000 inh−1 respectively. The weekly usage patterns between the four WWTPs differed probably due to the lifestyle of the populace serving the different WWTPs. These results provide useful data on illicit drug use in eThekwini that can be utilised by public health agencies to implement suitable response strategies.