Food insecurity (FI) is a modifiable social determinant of health that impacts approximately 10 percent of the U.S. population. FI has been linked to poorer health outcomes and higher healthcare costs. Given the prevalence of chronic health conditions in the United States, including serious mental illness (SMI), the current study aims to better understand the relationship between FI and chronic conditions, including SMI, in a nationally representative sample. Authors analyzed data from the 2016 Medical Expenditure Panel Survey household component and food security supplement. Findings indicate the prevalence of FI among those with diabetes, lung disease, stroke, and SMI is higher than among the general population, with the prevalence for those with SMI being particularly high (43 percent of the sample). Logistic regression models indicate strong, statistically significant relationships between FI and chronic conditions, including SMI, as well as FI and two or more chronic illnesses, even when controlling for sociodemographic and health factors. There are likely bidirectional relationships between FI and chronic conditions. Findings have implications for social workers, in relation to prevention and treatment of SMI and FI through direct care, advocacy, and integrated services in health, mental health, and social services.