With China’s rapid industrialization and urbanization, sustainable urban development is one of the most significant challenges that the country will face in the future, and the rational evaluation and improvement of urban land-use efficiency (ULUE) are becoming crucial for land and urban development. Existing studies rarely examine ULUE, and there is a dearth of urban land use analysis in terms of different functions, regional differences in levels of development, and innovation capacity. Therefore, we take the Pearl River Delta (PRD), China’s economic and innovation center, as our research target and propose a new framework to analyze its comprehensive ULUE. First, we summarized the patterns of land-use change in the PRD region as a whole along with nine major cities from 2000 to 2020 on the basis of data from the China Land Survey. Then, we constructed a multidimensional evaluation model for ULUE and analyzed the spatial differences and causes of multidimensional performance in nine major cities. Finally, we calculated the innovation capability index of the PRD region and established a coupling coordination–evaluation model to analyze the coordination relationship between innovation capability and urban land use. The three main findings of this study are as follows. (1) The growth rate of urban land in the PRD region as a whole exhibited stage differences. (2) The comprehensive ULUE in the PRD urban agglomeration was high, and the spatial variability of functional performance in each dimension was obvious. (3) The level of coordination between innovation capability and urban land use in the PRD region was high, and the coupled coordinated development exhibited a decreasing spatial distribution pattern. Thus, the PRD region mainly relies on the cities of Shenzhen and Guangzhou to drive innovation development of the region.