Introduction African Americans, especially those in the South, suffer a disproportionate burden of obesity and are at high risk for perceived discrimination (PD). This study investigates the association between PD and weight status among African Americans and clarifies the role of perceived stress and health behaviors in this relationship. Methods Data came from the Jackson Heart Study, Examination 1 (2000–2004; analyses conducted in 2016 using Stata, version 14). African Americans from Jackson, Mississippi, aged 21–95 years were recruited (N=5,301). Weight status was measured using anthropometric data with BMI; waist circumference (in centimeters); and obesity class (I, II, III). Survey instruments were used to measure PD, perceived global stress, and health behaviors. Multivariate regression was used to model weight status outcomes as a function of PD, perceived stress, and health behaviors. Results After controlling for sociodemographic factors and health status, perceived everyday discrimination was associated with higher BMI (b=0.33, p<0.01); higher waist circumference (b=0.70, p<0.01); and higher relative risk of Class III obesity versus non-obesity (relative risk ratio, 1.18; p<0.001). Global perceived stress was linked to higher BMI (b=0.42, p<0.05) and higher waist circumference (b=1.18; p<0.01) and partially mediated the relationships between PD and these weight status outcomes. Health behaviors led to suppression rather than mediation between PD and weight status and between stress and weight status. Conclusions PD and perceived stress are potential risk factors for higher weight status. They should be considered as a part of a comprehensive approach to reduce obesity among African Americans.