This application provides isolated antibodies, and antigen-binding fragments thereof, that specifically bind Programmed Death Ligand-1 (PD-L1). These PD-L1 antibodies, or antigen-binding fragments thereof, have a high affinity for PD-L1, function to inhibit PD-L1, are less immunogenic compared to their unmodified parent antibodies in a given species (e.g., a human), are capable of increasing T-cell proliferation and IL-2 secretion in a mixed lymphocyte reaction, and can be used to treat human diseases (e.g., cancer, infectious diseases, autoimmune diseases, asthma, transplant rejection, and inflammatory disorders).