This study proposes a data-driven operational control framework using machine learning-based predictive modeling with the aim of decreasing the energy consumption of a natural gas sweetening process. This multi-stage framework is composed of the following steps: (a) a clustering algorithm based on Density-Based Spatial Clustering of Applications with Noise methodology is implemented to characterize the sampling space of all possible states of the operation and to determine the operational modes of the gas sweetening unit, (b) the lowest steam consumption of each operational mode is selected as a reference for operational control of the gas sweetening process, and (c) a number of high-accuracy regression models are developed using the Gradient Boosting Machines algorithm for predicting the controlled parameters and output variables. This framework presents an operational control strategy that provides actionable insights about the energy performance of the current operations of the unit and also suggests the potential of energy saving for gas treating plant operators. The ultimate goal is to leverage this data-driven strategy in order to identify the achievable energy conservation opportunity in such plants. The dataset for this research study consists of 29 817 records that were sampled over the course of 3 years from a gas train in the South Pars Gas Complex. Furthermore, our offline analysis demonstrates that there is a potential of 8% energy saving, equivalent to 5 760 000 Nm(3) of natural gas consumption reduction, which can be achieved by mapping the steam consumption states of the unit to the best energy performances predicted by the proposed framework.