Introduction: Very little is known about the longitudinal associations between physical activity and obesity in Latin America. Therefore, the purpose of this study was to investigate associations of leisure-time physical activity with abdominal and general obesity in adults in Mexico. Methods: Participants in the Mexico City Prospective Study were surveyed from 1998 to 2004 and resurveyed from 2015 to 2019. Leisure-time physical activity volume at baseline was categorized as none or low or, alternatively, medium or high. Abdominal obesity at resurvey was defined as waist circumference ≥88 cm in women and ≥102 cm in men, while general obesity as BMI ≥30 kg/m2. Logistic regression models were adjusted for sociodemographic and lifestyle factors. Sensitivity analyses were also conducted in people who had never smoked and using different obesity scenarios. Results: The analysis included 9,782 adults aged 51 (11) years at baseline (mean [SD]). There were 6,818 cases of abdominal obesity and 2,964 cases of general obesity at resurvey. Compared with the group that reported little or no leisure-time physical activity, the OR (95% CI) for abdominal obesity was 0.86 (0.76, 0.98), and the OR for general obesity was 0.85 (0.75, 0.96) in the group that reported medium or high leisure-time physical activity. Similar associations were observed in participants who never smoked and in some of the obesity scenarios. Conclusions: This novel study suggests that leisure-time physical activity is associated with reduced risk of both abdominal and general obesity in adults in Mexico.