Objective: This study investigated the sex difference in prevalence of depression at 90 days after first-ever stroke. Methods: Patients with first-ever stroke (n = 786) were identified from the population-based Brain Attack Surveillance in Corpus Christi project (2011–2016). Poststroke depressive symptoms were assessed by the 8-itemPatient Health Questionnaire, and prestroke depression status (history and medication use) was self-reported. Logistic regression was used to examine the association between sex and depression after stroke, and effect modification by prestroke depression status, accounting for missing data. Results: Women were more likely to have a history of and be on medication for depression at the time of stroke than men (p < 0.001). Prevalence of depression at 90 days was 28.2% for men (95% confidence interval [CI], 23.7%–32.8%) and 32.7% for women (95% CI, 27.8%–37.5%). The age-adjusted odds ratio (OR) of depression after stroke comparing women with men was 1.34 (95% CI, 0.97–1.85), and fully attenuated after adjustment for sociodemographic, stroke, and prestroke characteristics. Effect modification by prestroke depression status was present (p = 0.038). Among participants on medication for depression at the time of stroke, women were significantly less likely to have depression at 90 days compared with men (OR, 0.39; 95% CI, 0.16–0.96); whereas significant sex differences were not noted among those with and without a depression history. Conclusion: The sex difference in prevalence of depression at 90 days after first-ever stroke was not significant overall, but varied by prestroke depression status. Interventions to address and prevent poststroke depression are needed, particularly among those with prestroke depression but not undergoing treatment for depression at stroke onset.