Background <p>One out of four persons may develop mental disorders during their lives. Women and the poor are particularly vulnerable. Research has shown that the prevalence of postpartum depression among women is between 5% and 26% with prevalence even higher in developing countries. However, studies on this condition in Ghana are few in literature. This current study assessed the prevalence and predictors of postpartum depression among postnatal women in Kumasi, Ghana.</p> Methods <p>A descriptive cross-sectional study design utilizing a quantitative approach was used to conduct the study at the postnatal clinics of three selected hospitals in the Kumasi city. A multistage sampling procedure was used to select 250 postnatal women for the study. Data were gathered from the respondents through a validated Edinburg Postnatal Depression Scale. Data were analysed with SPSS version 25.0 and statistical significance was established at <i>P</i> ≤ 0.05.</p> Results <p>Generally, 74.5%, 64% and 75% of the respondents had good knowledge about the risk factors; signs and symptoms; and consequences of postpartum depression respectively. The overall prevalence of postpartum depression in the selected hospitals was 14%. Regarding specific depressive symptoms, 14% of the respondents could never laugh and see the funny side of things. Maternal age (<i>P</i> = 0.002), postpartum blues (<i>P</i> = 0.000) and mode of delivery (<i>P</i> = 0.001) were significantly associated with PPD.</p> Conclusion <p>Postnatal women in Kumasi had good level of knowledge about PPD. However, gaps in knowledge were found with respect to specific signs and symptoms of PPD such as crying spells, overwhelming fatigue and insomnia. Predictors such as maternal age, partners’ support, perceived partners’ violence/abuse, and postpartum blues influenced the prevalence of PPD among the women. Healthcare providers should encourage family members and partners to provide the requisite support to mothers before, during and after childbirth.</p>