Regulatory agencies require testing of chemicals and products to protect workers and consumers from potential eye injury hazards. Animal screening, such as the rabbit Draize test, for potential environmental toxicants is time-consuming and costly. Therefore, virtual screening using computational models to tag potential ocular toxicants is attractive to toxicologists and policy makers. We have developed quantitative structure-activity relationship (QSAR) models for a set of small molecules with animal ocular toxicity data compiled by the National Toxicology Program Interagency Center for the Evaluation of Alternative Toxicological Methods. The data set was initially curated by removing duplicates, mixtures, and inorganics. The remaining 75 compounds were used to develop QSAR models. We applied both k nearest neighbor and random forest statistical approaches in combination with Dragon and Molecular Operating Environment descriptors. Developed models were validated on an external set of 34 compounds collected from additional sources. The external correct classification rates (CCR) of all individual models were between 72 and 87%. Furthermore, the consensus model, based on the prediction average of individual models, showed additional improvement (CCR = 0.93). The validated models could be used to screen external chemical libraries and prioritize chemicals for in vivo screening as potential ocular toxicants.