Understanding diabetes-specific quality of life (DSQOL) is important to improving lives of people with type 2 diabetes mellitus (T2DM). Despite the prevalence of T2DM among African Americans, there is scant evidence about DSQOL in this population. This study aims to understand relationships between DSQOL and demographics, clinical markers, psychosocial factors, and stress in African Americans. We hypothesize that: 1) predictors of DSQOL in African Americans will be consistent with predictors identified in prior studies with non-African Americans, and 2) greater stress will independently predict poorer DSQOL. Participants were 211 low-income African Americans with uncontrolled T2DM. The two hypotheses were tested using distinct linear regression models. Significant predictors of poorer DSQOL were: 1) fewer years of school, 2) fewer T2DM-related complications, 3) longer T2DM duration, and 4) more perceived stress. Findings suggest that interventions targeting stress could improve DSQOL in African Americans.