Waste-picking is an income-generating opportunity for individuals living in poverty. Waste picking is associated with a range of risk factors for common mental disorders (CMD). This study aimed to determine the prevalence and factors associated with CMD among waste pickers in Johannesburg. A cross-sectional study analyzed secondary data for 365 waste pickers. A validated Self-Reporting Questionnaire (SRQ-20) was used to assess CMD. Multivariable logistic regression was fitted to identify factors associated with CMD. The overall prevalence of CMD among waste pickers was 37.3%. The odds of having CMD were 2.5 and 3.2 higher in females and cigarette smokers, respectively (p = 0.019 and p = 0.003). Life enjoyment (Adjusted odds ratio [aOR] 0.54, p = 0.02) and a good quality of life (aOR 0.34, p ≤ 0.001) were associated with lower odds of CMD. The high prevalence of CMD among waste pickers was significantly associated with cigarette smoking, being female, not enjoying life, and a poor quality of life. Mental health awareness of CMD will assist with the prevention, early detection, and comprehensive management of CMD among waste pickers.