Purpose: Tubal ligation has been associated with reduced risk of epithelial ovarian cancer (EOC) in studies of primarily white women, but less is known about the association in African American (AA) women. We sought to evaluate the associations among 597 invasive ovarian cancer cases and 742 controls of AA descent recruited from the African American Cancer Epidemiology Study, a population-based case–control study in 11 geographical areas in the US. Methods: Multivariable logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals (CI) adjusted for potentially confounding factors. Results: An inverse association between tubal ligation and EOC was observed that was not statistically significant (OR 0.88, 95% CI 0.68–1.14). However, an inverse association with EOC risk was observed among women who had a tubal ligation at age 35 years or older (OR 0.64; 95% CI 0.41–0.98), but not among those who had a tubal ligation before age 35 (OR 0.98; 95% CI 0.74–1.29) (p for interaction = 0.08). The association also varied considerably by tumor subtype. A strong inverse association was observed for endometrioid tumors (OR 0.31, 95% CI 0.14–0.70), whereas associations with mucinous (OR 0.87, 95% CI 0.36–2.12) and serous (OR 0.94, 95% CI 0.71–1.24) tumors were weaker and not statistically significant. A statistically non-significant positive association for clear cell tumors (OR 1.84, 95% CI 0.58–5.82) was based on a low number of cases. Conclusions: Our findings show that tubal ligation may confer a reduced risk for EOC among AA women that is comparable to the associations that have been previously observed in primarily white populations.