A vital avenue through which replacing coal with shale gas in the energy system reshapes the feedstock of China's chemical manufacturing and related environmental burdens. Here, we use ethylene glycol production as an example to evaluate the environmental loads from four typical production routes—naphtha to ethylene glycol (OEG), ethane to ethylene glycol (EEG), coal-based methanol to ethylene glycol (MEG), and coal-based syngas to ethylene glycol (CEG)—by life-cycle assessment method based on global nine midpoint impacts and China's localized energy conservation and emission reduction (ECER) index. The result shows that replacing the traditional coal-fed MEG and CEG capacity with ethane-fed EEG capacity reduces most environmental stresses but increases ODP and POFP burdens by 87% and 21%, respectively. Furthermore, the scenario analysis shows that feedstock change and production growth referring to the 2018 baseline increase the environmental burdens of China's ethylene glycol industry by 20–170% by 2025. This study updates the environmental-burden picture of ethylene glycol production under the dual contexts of the energy system and chemical feedstock transitions to achieve sustainable development for policymakers.