Food insecurity (FI) contributes to HIV-related morbidity and mortality, but the mechanisms whereby FI negatively impacts HIV health are untested. We tested the hypothesis that FI leads to poor HIV clinical outcomes through nutritional, mental health, and behavioral paths. We analyzed data from Women’s Interagency HIV Study (WIHS) among 1803 women living with HIV (WLWH) (8225 person-visits) collected from 2013 to 2015 biannually from nine sites across the United States participating in the WIHS. FI was measured with the US Household Food Security Survey Module. Outcomes included HIV viral nonsuppression, CD4 cell counts, and physical health status (PHS). We used longitudinal logistic and linear regression models with random effects to examine associations adjusting for covariates and path analysis to test nutritional, mental health, and behavioral paths. Increasing severity of FI was associated with unsuppressed viral load, lower CD4 counts, and worse PHS (all p < 0.05). Report of FI 6 months earlier was independently associated with most outcomes after adjusting for concurrent FI. For viral nonsuppression, the nutritional and behavioral paths accounted for 2.09% and 30.66% of the total effect, with the mental health path operating via serial mediation through the behavioral path. For CD4 count, the mental health and behavioral paths accounted for 15.21% and 17.0% of the total effect, respectively. For PHS, depressive symptoms accounted for 60.2% of the total effect. In conclusion, FI is associated with poor health among WLWH through different paths depending on the outcome. Interventions should target FI and its behavioral and mental health mechanisms to improve HIV outcomes.