Objective: This study aimed to evaluate the association between obesity and cognitive impairment. Methods: This study is a sub-analysis of an observational, cross-sectional study in nine Latin American counties. Sociodemographic, clinical and anthropometric data were collected, and cognition was assessed using the Montreal Cognitive Assessment (MoCA) tool in 722 postmenopausal women. Results: The mean age, body mass index (BMI) and years of education of the cohort were 56.9 years, 26.8 kg/m2 and 13.6 years, respectively. Women with cognitive impairment, compared to those without, had a higher BMI (27.8 ± 5.9 vs. 26.6 ± 4.9 kg/m2, p = 0.037), had more children (3.1 ± 2.4 vs. 2.5 ± 1.7, p = 0.023), experienced more severe menopausal symptoms (56.3% vs. 31.9%, p < 0.001) and presented more comorbidities (60.0% vs. 43.8%, p = 0.006). They also had fewer years of study (10.8 ± 5.1 vs. 13.9 ± 4.9 years, p = 0.001), were less physically active (35.0% vs. 49.1%, p = 0.018) and were less likely to use menopausal hormone therapy (MHT) (11.3% vs. 28.8%, p = 0.001). In binary logistic regression analysis, BMI ≥ 35.0 kg/m2 (odds ratio [OR] 2.27, 95% confidence interval [CI] 1.08–4.76) and severe menopausal symptoms (OR 2.10, 95% CI 1.29–3.43) were associated with cognitive impairment. In the model, factors related to lower risk were ever use of MHT (OR 0.44, 95% CI 0.21–0.92) and having more years of education (OR 0.38, 95% CI 0.20–0.64). Conclusion: Severe obesity and severe menopausal symptoms increased the risk of cognitive impairment in postmenopausal women, while higher education and ever use of MHT were protective factors.