Background: Emerging research suggests that the novel coronavirus disease (COVID-19) pandemic and associated public health restrictions have caused psychological distress in many contexts. In order for public health authorities and policy makers to effectively address the psychological distress associated with the pandemic, it is important to determine the prevalence and correlates of mental disorders, including depression. Objectives: We aimed to determine the prevalence, and demographic, social, clinical and other COVID-19 related correlates of major depressive disorder symptoms among the general population in Ghana during the COVID-19 pandemic. Method: The study was a cross-sectional survey using online data collection methods. The survey assessed demographic, social and clinical variables as well as COVID-19 related variables. Major depressive disorder symptoms were assessed using the Patient Health Questionnaire-9. The survey link was distributed primarily through WhatsApp-based platforms. Data were analyzed using descriptive and inferential statistics. Results: The overall prevalence of likely MDD symptoms among the sample population was 12.3%. Variables such as employment, loss of jobs during the pandemic and rate of exposure to COVID-related news were independently and significantly associated with the likelihood that respondents had likely MDD. Variables such as gender, relationship, housing status and having a family member or friend who was sick from COVID-19 were not independently significantly associated with the likelihood that respondents had likely MDD, when all other factors in the model were controlled. Conclusion: This study has identified the prevalence and correlates of depression symptoms in Ghana during the COVID-19 pandemic. There is the urgent need for mental health policy makers and the government of Ghana to have policies in place to alleviate the potential threat to the mental health of the population.