Objective: We investigated the association between prenatal selective serotonin reuptake inhibitors (SSRI) exposure and pregnancy-outcomes with correlation to placental-histopathology. Study design: Included were pregnancies with maternal SSRI use throughout pregnancy (SSRI-group) and the control group was matched with pregnancies unexposed to SSRI. Placental lesions were classified according to the “Amsterdam” criteria. Adverse neonatal outcome was defined as ≥1 early neonatal-complications. Results: SSRI group had lower birthweights (p < 0.001), higher rates of meconium (p = 0.009), NICU admissions (p < 0.001), and adverse neonatal-outcome (p < 0.001). SSRI placentas had lower birthweight-to-placental-weight ratio (p = 0.02) and higher rates of fetal vascular malperfusion (FVM) lesions (p = 0.03). Using multivariable analyses: GA < 37 weeks (aOR = 2.1, 95%CI 1.7–4.6) and SSRI (aOR = 1.7, 95%CI 1.3–3.9) were independently associated with adverse neonatal outcome while GA < 37 weeks (aOR = 1.6, 95%CI 1.2–3.4), SSRI (aOR = 1.3, 95%CI 1.1–2.6), and smoking (aOR = 1.2, 95%CI 1.1–4.0) were independently associated with FVM lesions. Conclusion: SSRI use during pregnancy was independently associated with adverse neonatal outcome and placental FVM.