This study explored clinical and sociodemographic moderators of treatment response to “Be a Mom”, an internet-based cognitive behavioral therapy (iCBT) intervention, from baseline to postintervention, in women at high risk for postpartum depression (PPD). The study also assessed the stability of women’s treatment gains from baseline to 4-months postintervention (follow-up). This open-label randomized controlled trial (RCT) involved a sample of 1,053 postpartum Portuguese women identified as being at high risk for PPD (i.e., having a score of 5.5 or higher on the Postpartum Depression Predictors Inventory-Revised); participants were allocated to “Be a Mom” intervention group or a waiting-list control group, and completed self-report measures at baseline, postintervention, and a 4-month follow-up (554 women completed follow-up assessments). Depressive and anxiety symptoms were measured using the Edinburgh Postnatal Depression Scale and the anxiety subscale of the Hospital Anxiety and Depression Scale, and flourishing/positive mental health was assessed with the Mental Health Continuum. Regression models and linear mixed models were used to examine moderators of treatment and the mid-term efficacy of the “Be a Mom” intervention, respectively. The results revealed that treatment completion, higher depression scores at baseline, and higher income levels were linked to greater symptom reduction and positive mental health enhancement. Moreover, the efficacy of the “Be a Mom” intervention was supported at the 4-month follow-up. The “Be a Mom” intervention appears to be an effective iCBT tool for reducing psychological distress and enhancing positive mental health in women at risk for PPD, with therapeutic improvements maintained over a 4-month period.