Understanding information on the regional water–energy–food system pressure (WEFSP) is crucial for ensuring resource security and promoting sustainable regional development. Existing studies often lack a focus on water quality issues, which cannot fully reveal the current situation of WEFSP. This study incorporated the grey water footprint as a measurement indicator to integrate water quality into the WEF nexus, re-examining the WEFSP across 30 Chinese provinces from 2006 to 2020. The spatiotemporal evolutionary characteristics of the WEFSP were characterized using Standard Deviation Ellipse (SDE) and Kernel Density Estimation (KDE). Furthermore, the GeoDetector method was employed to identify the key driving factors and their interactive effects. The results revealed that (1) China’s WEFSP initially increased and then decreased, and the WEFSP changes the most during the five-year plan transition period. The energy subsystem was under the greatest pressure, while water quality scarcity caused by pollution was the dominant driver of pressure within the water subsystem. (2) Spatially, the WEFSP exhibited an east-high and west-low pattern, with the center of gravity of the WEFSP mainly located in Anhui and Henan provinces, and during the study period, it experienced two stages of transfer: from northwest to southeast and vice versa. (3) The explanatory power of driving factors for the spatial heterogeneity of the WEFSP exhibited dynamic variability. The most influential factor shifted from annual average precipitation to per capita consumption expenditure. Significant interactive effects were identified among factors, all demonstrating either bilateral or nonlinear enhancement. These findings provide a comprehensive insight into the current state of WEFSP and the influence of external factors, offering a scientific basis for formulating targeted resource management strategies to ensure the security of the WEF nexus.