Ovarian cancer accounts for more deaths than any other cancer of the female reproductive system. Patients who have ovarian tumors infiltrated with high frequencies of T cells are associated with a greater survival probability. However, therapies to revitalize tumor-associated T cells, such as PD-L1/PD-1 or CTLA4 blockade, are ineffective for the treatment of ovarian cancer. In this study, we demonstrate that for ovarian cancer, Toll-Like Receptor 5 (TLR5) signaling, for which the only known ligand is bacterial flagellin, governed failure of PD-L1 and CTLA4 blockade. Mechanistically, chronic TLR5 signaling on CD11c+ cells in vivo and in vitro impaired the differentiation of functional IL-12-producing XCR1+CD103+ conventional type 1 dendritic cells (cDC1), biasing CD11c+ precursor cells toward myeloid subsets expressing high levels of PD-L1. This culminated in impaired activation of CD8+ T cells, reducing CD8+ T-cell function and ability to persist within the ovarian tumor microenvironment. Expansion of cDC1s in situ using FLT3L in combination with PD-L1 blockade achieved significant survival benefit in TLR5 knockout mice bearing ovarian tumors, whereas no benefit was observed in the presence of TLR5 signaling. Thus, we have identified a host-intrinsic mechanism leading to the failure of PD-L1 blockade for ovarian cancer, demonstrating that chronic TLR5 signaling on CD11c+ cells is a barrier limiting the efficacy of checkpoint therapy.