Antimony chalcogenides Sb2Se3 and Sb2S3 are an emerging class of quasi-one-dimensional van der Waals bonded materials with rapid progress and great promise for low-cost, high-efficiency, and scalable thin-film photovoltaics. Here using first-principles theoretical calculations, we show that antimony chalcogenides Sb2Se3 and Sb2S3 possess competing superior electronic structure and complex defect chemistry, limiting their photovoltaic performance. The high optical absorption, large Born effective charge, and high dielectric constant lead to low exciton binding energy and small hole effective mass, which ultimately benefit the photovoltaic performance. In contrast, quasi-1D antimony chalcogenides exhibit complex defect chemistry. The cation–anion antisites are the dominating native defects in the Sb rich condition, while in the Sb poor condition the anion–cation antisites are dominant. In both cases, the anion vacancies are also easy to form. These native defects introduce midgap transition levels which act as electron–hole recombination centers, limit the dopability, and lower the open circuit voltage. As a result, Sb2Se3 is a p-type semiconductor in Se rich condition, while Sb2S3 is an intrinsic semiconductor without significant free carrier density. Additionally, due to the unique quasi-1D structures and strong electron–lattice coupling, antimony chalcogenides are able to accommodate larger lattice relaxation than conventional 3D bulk crystals, resulting in negative-U behavior in their defect structures. Therefore, the competing superior electronic structure and complex defect chemistry suggest that, while antimony chalcogenides are excellent photoabsorbers, effort shall be made to suppress the formation of the detrimental native defects to further improve their open-circuit voltage, electronic transport, and, thus, power conversion efficiency.