An estimated 78% of Hispanics in the United States (US) are overweight or obese. Household food insecurity, a condition of limited or uncertain access to adequate food, has been associated with obesity rates among Hispanic adults in the US. However, the Hispanic group is multi-ethnic and therefore associations between obesity and food insecurity may not be constant across Hispanic country of origin subgroups. This study sought to determine if the association between obesity and food insecurity among Hispanics is modified by Hispanic ancestry across low-income (≤200% of poverty level) adults living in California. Data are from the cross-sectional 2011–12 California Health Interview Survey (n = 5498). Rates of overweight or obesity (BMI ≥ 25), Calfresh receipt (California's Supplemental Nutrition Assistance Program), and acculturation were examined for differences across subgroups. Weighted multiple logistic regressions examined if household food insecurity was significantly associated with overweight or obesity and modified by country of origin after controlling for age, education, marital status, country of birth (US vs. outside of US), language spoken at home, and Calfresh receipt (P < .05). Significant differences across subgroups existed for prevalence of overweight or obesity, food security, Calfresh receipt, country of birth, and language spoken at home. Results from the adjusted logistic regression models found that food insecurity was significantly associated with overweight or obesity among Mexican-American women (β (SE) = 0.22 (0.09), p = .014), but not Mexican-American men or Non-Mexican groups, suggesting Hispanic subgroups behave differently in their association between food insecurity and obesity. By highlighting these factors, we can promote targeted obesity prevention interventions, which may contribute to more effective behavior change and reduced chronic disease risk in this population.