Adverse childhood experiences (ACEs) are a critical determinant and predictor of health across the lifespan. The Appalachian region of the United States, particularly the central and southern portions, experiences worse health outcomes when compared to the rest of the nation. The current research sought to understand the cross-sectional relationships between ACEs, social determinants of health and other health risk factors in one southcentral Appalachian state. Researchers used the 2012 and 2014 North Carolina Behavioral Risk Factor Surveillance System (BRFSS) for analyses. An indicator variable of Appalachian county ( = 29) was used to make comparisons against non-Appalachian counties ( = 71). Analyses further examined the prevalence of ACEs in households with and without children across Appalachian and non-Appalachian regions, and the effects of experiencing four or more ACEs on health risk factors. There were no statistically significant differences between Appalachian and non-Appalachian counties in the prevalence of ACEs. However, compared with adults in households without children, those with children reported a higher percentage of ACEs. Reporting four or more ACEs was associated with higher prevalence of smoking (prevalence ratio [PR] = 1.56), heavy alcohol consumption (PR = 1.69), overweight/obesity (PR = 1.07), frequent mental distress (PR = 2.45), and food insecurity (PR = 1.58) in adjusted models and with fair or poor health only outside Appalachia (PR = 1.65). Residence in an Appalachian county was independently associated with higher prevalence of food insecurity (PR = 1.13). Developing programs and implementing policies aimed at reducing the impact of ACEs could improve social determinants of health, thereby helping to reduce health disparities.