Sustainable water utilization is the basis of sustainable development and is crucial to the realization of UN sustainable development goals. It is necessary to assess the progress of sustainable water utilization using a comprehensive framework concerning both water quantity and quality. Our work constructed a framework WRWGF (Water Resource-Withdrawal-GDP-Footprint) articulating water quantity with water quality based on grey water footprint (GWF), and investigated the sustainable water utilization of cities in China's largest economic province——Guangdong which suffers from severe water pollution. Findings showed that the GWF of Guangdong decreased from 156.46 to 133.72 Gm3/y with fluctuation from 2008 to 2018, and the GWFs of cities presented higher in the Pearl River Delta (PRD) urban agglomeration, as well as the higher level of grey water stress. Sustainable water utilization of most cities showed climbing trends with fluctuation, and provincial sustainable water utilization achieved great improvement after 2015 driven by stricter water regulations. Wastewater disposal rate was the major driver of sustainable water utilization in most cities. The GWF indicator should be incorporated into current water management focusing on mitigating water shortage and pollution that tailored to local conditions based on development levels, contributing to the overall improvement in sustainable water utilization across Guangdong. The study proposed an integrated framework to assess the sustainable water utilization from a holistic view, aiming at providing a scientific basis for water management towards regional sustainability.