Food insecurity is a significant public health issue that affects the physical and mental health of people of all ages. Higher levels of self-efficacy may reduce levels of food insecurity. In addition, acculturation is potentially an important factor for food insecurity among immigrant populations. The purpose of this study is to examine food insecurity associated with self-efficacy and acculturation among low-income primary care patients in the United States. A self-administered survey was administered in May and June 2015 to uninsured primary care patients (N = 551) utilizing a free clinic that provides free primary care services to low-income uninsured individuals and families in the United States. On average, participants reported low food security. Higher levels of self-efficacy were associated with lower levels of food insecurity. Higher levels of heritage language proficiency were related to lower levels of food insecurity. US-born English speakers, women, and unmarried individuals potentially have higher risks of food insecurity and may need interventions to meet their specific needs. Self-efficacy should be included in nutrition education programs to reduce the levels of food insecurity. Future studies should further examine why these groups have a high risk to better understand needs for interventions.