Objective: This study explored how experiences of stress in adulthood, including the occurrence of stressful life events and psychosocial strains in various life domains, might be related to stress-related eating and indicators of obesity, including body mass index (BMI) and waist circumference. Method: Cross-sectional data were examined from 3,708 adults in the Midlife in the U.S. study (MIDUS II). Results: Hierarchical regression analyses indicated that experiences of stress were associated with higher BMI and waist circumference, even after controlling for age, annual household income, education level, race, and sex, although the additional variance accounted for was small. A nonparametric bootstrapping approach indicated that stress-related eating mediated the association between experiences of stress and indicators of obesity. Moderated-mediation analyses indicated that the relationship between experiences of stress and stress-related eating was amplified for women and individuals with obesity in comparison to men and individuals without obesity. Mindfulness did not moderate the experiences of stress and stress-related eating association. Conclusions: These results provide further evidence of the contributions of psychosocial factors to chronic disease risk.