Health care systems are increasingly adopting methods to screen for and integrate food insecurity and other social risk factors into electronic health records. However, there remain knowledge gaps regarding the cumulative burden of food insecurity in large clinical settings, which patients are most at risk, and the extent to which patients are interested in social assistance through their health care system. To evaluate the 5-year prevalence and associated risk factors of food insecurity among adult primary care patients, and to examine factors associated with patients' interest in social assistance among those with food insecurity. This cross-sectional analysis of a retrospective cohort study took place at a tertiary care academic medical center (encompassing 20 primary care clinics) in Michigan. Participants included adult patients who completed screening for social risk factors between August 1, 2017, and August 1, 2022. Data analysis was performed from November 2022 to June 2023. Food insecurity was assessed using the Hunger Vital Sign. The primary outcome was patients' interest in social assistance, and associated factors were examined using multivariate logistic regression models, adjusting for patients' demographic and health characteristics. Over the 5-year period, 106 087 adult primary care patients (mean [SD] age, 52.9 [17.9] years; 61 343 women [57.8%]) completed the standardized social risk factors questionnaire and were included in the analysis. The overall prevalence of food insecurity was 4.2% (4498 patients), with monthly trends ranging from 1.5% (70 positive screens) in August 2018 to 5.0% (193 positive screens) in June 2022. Food insecurity was significantly higher among patients who were younger, female, non-Hispanic Black or Hispanic, unmarried or unpartnered, and with public health insurance. Food insecurity was significantly associated with a higher cumulative burden of social needs, including social isolation, medical care insecurity, medication nonadherence, housing instability, and lack of transportation. Only 20.6% of patients with food insecurity (927 patients) expressed interest in social assistance. Factors associated with interest in social assistance including being non-Hispanic Black, unmarried or unpartnered, a current smoker, and having a higher burden of other social needs. In this retrospective cohort study, the overall prevalence of food insecurity was 4.2%, of whom approximately 1 in 5 patients with food insecurity expressed interest in assistance. This study highlights ongoing challenges in ensuring all patients complete routine social determinants of health screening and gaps in patients' interest in assistance for food insecurity and other social needs through their health care system.