Perinatal mental health is a major public health issue that arises during pregnancy and/or after birth, with substantial implications for social, parental, and maternal functioning, as well as overall quality of life. The study aimed to determine the prevalence of perinatal depression and its associated risk factors among women who visited a maternity hospital in Kathmandu, Nepal. A cross-sectional study was conducted at the Paropakar Maternity and Women's Hospital in Kathmandu. A total of 300 women in their perinatal period were interviewed. The Edinburgh Perinatal Depression Scale (EPDS) was used to measure perinatal depression. The Poisson regression model was used to determine risk factors associated with perinatal depression. The mean age of respondents was 25.5 (SD 4.5) years; average age during their first pregnancy was 23.5 (SD 3.7) years; and 53.7% of respondents were in the antenatal period. The prevalence of depressive symptoms (EPDS ≥ 10) was 40% (95% CI 31.4% to 45.8%). Unsupportive family members (adjusted prevalence ratio [aPR] 2.23; 95% CI 1.75-2.86), postnatal period (aPR 2.64; 95% CI 1.97-3.53), complications faced during delivery (aPR 1.76; 95%CI 1.30-2.39), history of intimate partner violence (aPR 0.48; 95% CI 0.36-0.64), and first pregnancy at the age of ≤25 years (aPR 0.61; 95% CI 0.42-0.88) were identified as key risk factors of perinatal depression. Strong family support and the active involvement of partners in counselling can contribute to alleviating perinatal depression symptoms. Targeted interventions in health and well-being services should be implemented to address mental health burden during both pregnancy and postpartum periods.