The benefit of PD-L1 blockade as an immunotherapy for malignancies intriguingly extends to PD-L1 negative tumors, suggesting that non-tumor cells contribute to PD-L1 expression in the tumor microenvironment (TME). Natural killer (NK) cells, vital mediators of innate immunity, vigorously express PD-L1 upon activation. We demonstrate that the ligation of PD-L1 on circulating and solid tumor-infiltrating NK cells with the therapeutic anti-PD-L1 antibody atezolizumab, soluble PD-1, or PD-1 expressed by surrounding T cells or tumor cells leads to enhanced NK cell-mediated tumor clearance via changes in metabolism, adhesion, and migration. PD-L1 engagement increases NK cell infiltration into tumors via the CXCR3 pathway and induces alterations in cytoskeletal dynamics, which are supported by a metabolic shift in NK cells from glycolysis to fatty acid oxidation (FAO). Loss of CPT1A, a gatekeeping enzyme for FAO, in NK cells abrogates the PD-L1-mediated anti-tumor effect, supporting a critical role for FAO in enhanced NK cell killing. The PD-L1-triggered shift away from glycolysis permits NK cells to remain highly effective at tumor killing in glucose-restricted TME. Taken together, PD-L1 ligation enhances NK cell cytotoxicity and tumor infiltration and contributes to NK resilience in challenging TME conditions, resulting in a more effective anti-tumor immunity.