Objective To preliminarily assess the ameliorative effect of Mom’s Good Mood (MGM) on the prevalence of antenatal depression based on a pilot study, and to provide evidence for a scale-up study. Methods This study was conducted in Ma’anshan Maternal and Child Health Center as a pilot study of an implementation study conducted in China called the Perinatal Depression Screening and Management (PDSM) program. In 2019, 1 189 participants (gestational week ≤14+6 weeks) were included in the implementation group. Females were recruited in the first trimester and followed up in the second and third trimesters. At each time point, the participants’ depression status was screened by the Edinburgh postpartum depression scale (EPDS), and those who were screened as having depression were provided the MGM intervention. In 2020, 1 708 participants who underwent screening with the EPDS in either the first, second or third trimester at Ma’anshan Maternal and Child Health Center were included in the control group. Mann‒Whitney U test, Chi-square, and multivariate logistic regression analysis were used to compare the EPDS scores and depression prevalence between the control and implementation groups to assess the ameliorative effect of MGM (screening and intervention) on antenatal depression. Results In the first trimester, there were no statistically significant differences in EPDS scores or depression prevalence between the two groups (P>0.05). In the second and third trimesters, both the EPDS scores and depression prevalence of the implementation group were lower than those of the control group (P<0.05). After adjusting for confounders, logistic regression analysis showed that the risks of depression in the implementation group in both the second and third trimesters were lower than those in the control group (ORsecond trimester=0.55, 95%CI 0.37 to 0.81, P=0.003; ORthird trimester=0.51, 95%CI 0.35 to 0.74, P<0.001). Conclusion Implementation of the MGM based on the primary care system can effectively reduce the prevalence of antenatal depression, providing evidence for further scale up.