Efficient urban land use plays a crucial role in promoting regional development and ensuring economic growth. Analyzing the spatio–temporal pattern of urban land high-quality use (ULHU) and identifying its key influencing factors and pathways can contribute to enhancing land use efficiency and achieving high-quality development. This study established a comprehensive measurement indicator system for evaluating ULHU using the entropy method and investigated the spatio–temporal evolution pattern of ULHU in the Pearl River Delta (PRD) urban agglomeration in the years 2005, 2010, 2015 and 2020. Furthermore, a multi-period fuzzy-set qualitative comparative analysis method was adopted to explore the concurrent driving mechanisms that impact ULHU from the configuration perspective. The findings reveal that the level of ULHU has exhibited a significant improvement, increasing from 0.1150 in 2005 to 0.2758 in 2020, with an annual growth rate of 8.739%. The spatial pattern in the PRD region exhibits an incremental distribution, characterized by higher values in the central region and lower values in the peripheral area, as this pattern reveals significant heterogeneity across the region. The configurations for ULHU in the PRD were identified, such as Population-industry-talent driven, Openness-fiscal-talent driven, Population-led, and Population-industry driven. Among these configurations, population density and industrial structure were identified as the core driving factors, while the role of talent resources is gradually diminishing. This study provides practical guidance for promoting the ULHU and optimizing national spatial planning.