Ammonia recovery from wastewater has positive environmental benefits, avoiding eutrophication and reducing production energy consumption, which is one of the most effective ways to manage nutrients in wastewater. Specifically, ammonia recovery by membrane distillation has been gradually adopted due to its excellent separation properties for volatile substances. However, the global optimization of direct contact membrane distillation (DCMD) operating parameters to maximize ammonia recovery efficiency (ARE) has not been attempted. In this work, three key operating factors affecting ammonia recovery, i.e., feed ammonia concentration, feed pH, and DCMD running time, were identified from eight factors, by a two-level Plackett-Burman Design (PBD). Subsequently, Box-Behnken design (BBD) under the response surface methodology (RSM) was used to model and optimize the significant operating parameters affecting the recovery of ammonia though DCMD identified by PBD and statistically verified by analysis of variance (ANOVA). Results showed that the model had a high coefficient of determination value (R2 = 0.99), and the interaction between NH4Cl concentration and feed pH had a significant effect on ARE. The optimal operating parameters of DCMD as follows: NH4Cl concentration of 0.46 g/L, feed pH of 10.6, DCMD running time of 11.3 h, and the maximum value of ARE was 98.46%. Under the optimized conditions, ARE reached up to 98.72%, which matched the predicted value and verified the validity and reliability of the model for the optimization of ammonia recovery by DCMD process.