Objective. This study examined differences in socio-demographic characteristics and health behaviors relevant to chronic medical conditions (CMCs) in the Mid-South region (Alabama, Mississippi, Louisiana, Kentucky, Tennessee, and Arkansas), and identified subpopulations with increased burden of chronic disease. Methods. Data were obtained from the 2013 Behavioral Risk Factor Surveillance System. The top five most prevalent CMCs in the Mid-South were analyzed: asthma, high blood pressure (HBP), obesity, arthritis, and depression. Adjusted odds ratios (AOR) and confidence intervals (CI) of race–gender combinations were estimated using logistic regression. Differences in associations between socio-demographic characteristics and CMCs according to income were also examined. Results. The weighted prevalence estimates of the top five CMCs ranged from 66% (asthma) to 20% (depression). Higher income and employment were associated with better outcomes in all five CMCs. Higher educational attainment and physical activity were associated with better HBP, obesity, and arthritis status. Black and white females had higher odds of asthma compared to white males (black AOR = 1.7, CI: 1.1–2.6, white AOR = 1.7, CI: 1.3–2.2). Black males had lower odds of arthritis (AOR = 0.8, CI: 0.6–0.9), while white females had higher odds (AOR = 1.3, CI: 1.2–1.4). Similarly, the odds of depression were lower among black males (AOR = 0.5, CI: 0.4–0.6) and higher among white females (AOR = 2.2, CI: 2.0–2.5). Income-related differences by race were observed for HBP and obesity. Conclusion. Disparities in CMCs are associated with income and disproportionately affect the black population. In the Mid-South, race and gender disparities in the top five chronic conditions are more prominent among higher-income rather than lower-income individuals.