The spatial structure of urban agglomeration reveals the self-organization process of internal factors from the outside. As China ushers into a critical stage with the boosting of urbanization and the booming of the economy, measuring the spatial structure of urban agglomerations is vital to urban planning, regional development, etc. Nighttime stable light data from the National Polar–Orbiting Partnership-Visible Infrared Imaging Radiometer Suite (NPP-VIIRS) night-time light (NTL) series dataset offers a novel source that potentially simulates spatial variations in socio-economic activities. The present study aimed to scientifically guide wide applications of the NPP-VIIRS data to define and measure the evolution of urban agglomeration from a spatial–temporal perspective. Yangtze River Middle Reaches (YRMR) Urban Agglomeration (UA) in Central China was taken as the case study region to systematically identify and measure its spatial configuration of urban growth. The light index model and the method of the rank clock were performed to quantify the dynamics of rank-order distributions. In the meantime, spatial statistics and location coefficient index were used to identify the nature and heterogeneity of spatial structure. According to our findings, NPP-VIIRS data can offer insights into the applications to analyze urbanization processes and reveal the dynamics of urban expansion. The proposed framework will help understand the nature and unbalance of spatial configurations of urban economic growth within urban agglomeration and lay a theoretical basis for the policy-making of regional spatial planning.