Hydrogen peroxide (H2O2) production in microbial electrochemical systems (MESs) is an attractive option for enabling a circular economy in the water/wastewater sector. Here, a machine learning algorithm was developed, using a meta-learning approach, to predict the H2O2 production rates in MES based on the seven input variables, including various design and operating parameters. The developed models were trained and cross-validated using the experimental data collected from 25 published reports. The final ensemble meta-learner model (combining 60 models) demonstrated a high prediction accuracy with very high R2 (0.983) and low root-mean-square error (RMSE) (0.647 kg H2O2 m−3 d−1) values. The model identified the carbon felt anode, GDE cathode, and cathode-to-anode volume ratio as the top three most important input features. Further scale-up analysis for small-scale wastewater treatment plants indicated that proper design and operating conditions could increase the H2O2 production rate to as high as 9 kg m−3 d−1.