Arsenic in drinking water is a serious threat for human health due to its toxic nature and therefore, its eliminating is highly necessary. In this study, the ability of different novel and robust machine learning (ML) approaches, including Light Gradient Boosting Machine (LightGBM), Extreme Gradient Boosting, Gradient Boosting Decision Tree, and Random Forest was implemented to predict the adsorptive removal of arsenate [As(V)] from wastewater over 13 different metal–organic frameworks (MOFs). A large experimental dataset was collected under various conditions. The adsorbent dosage, contact time, initial arsenic concentration, adsorbent surface area, temperature, solution pH, and the presence of anions were considered as input variables, and adsorptive removal of As(V) was selected as the output of the models. The developed models were evaluated using various statistical criteria. The obtained results indicated that the LightGBM model provided the most accurate and reliable response to predict As(V) adsorption by MOFs and possesses R2, RMSE, STD, and AAPRE (%) of 0.9958, 2.0688, 0.0628, and 2.88, respectively. The expected trends of As(V) removal with increasing initial concentration, solution pH, temperature, and coexistence of anions were predicted reasonably by the LightGBM model. Sensitivity analysis revealed that the adsorption process adversely relates to the initial As(V) concentration and directly depends on the MOFs surface area and dosage. This study proves that ML approaches are capable to manage complicated problems with large datasets and can be affordable alternatives for expensive and time-consuming experimental wastewater treatment processes.