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Abstract Background Diabetes and depression are both chronic debilitating conditions, and their coexistence has been associated with adverse outcomes. In this study, we investigated the association between glycaemic control and depression in type 2 diabetes (T2DM) patients attending a tertiary healthcare facility in Ghana. Methodology In a cross-sectional study design, Patient Health Questionnare-9 (PHQ-9) was used to assess depression in 400 T2DM, aged 30–65 years. Anthropometric characteristics and blood pressure were measured. Venous blood was collected to measure the levels of glycated haemoglobin (HbA1c). Results The prevalence of depression was 31.3% among T2DM patients. Female gender, being unmarried, frequent intake of alcohol, previous smoking status and insulin use were associated with increased odds of depression, whereas being educated above basic school level was associated with a decreased odds of depression. In a multivariable logistic regression model, being unmarried and poor glycaemic control were associated with an increase in odds of depression after adjusting for age, gender, and social factors. The association between depression and glycaemic control was attenuated when clinical factors were introduced into the model. Conclusion In our study population, we found that depression is common among Ghanaians with T2DM, and not associated with poor glycaemic control in a fully multivariable-adjusted model.