Background: Sociocultural factors play critical roles in the mental health of marriage-based immigrant women. However, the effect of bi-dimensional acculturation (“adaptation to host culture” and “maintenance of heritage culture”) and social support on perinatal depression across time was unknown among them. Objective: To examine the effect of bi-dimensional acculturation and social support on perinatal depression among marriage-based immigrant women in Taiwan. Methods: This longitudinal study recruited 310 immigrant mothers to complete structured questionnaires during pregnancy and postpartum periods. Depression was assessed using the Edinburgh Postnatal Depression Scale. Bi-dimensional acculturation was measured using the Bi-dimensional Acculturation Scale for Marriage-Based Immigrant Women. Social support was measured by a three-subscale instrument, namely emotional, instrumental, and informational support. Results: Depression scores increased from pregnancy to three months postpartum, and decreased from six to twelve months postpartum. The generalized estimating equation results showed that lower adaptation to host culture, emotional support, and informational support were associated with higher maternal depression scores over time. Maintaining heritage culture has both positive (from pregnancy to three months postpartum) and negative associations (from six to twelve months postpartum) with maternal depression, further, increased emotional support enhanced the protective effect of adaptation to host culture, but decreased the positive effect of maintenance of heritage culture on depression. Conclusion: Strategies should be developed to assist perinatal immigrant women to adapt to the host culture, maintain their heritage culture, and resolve potential cultural conflicts to decrease their depression. Respect for immigrant mothers' heritage cultures should be accompanied by increased emotional support.