Exploring the heterogeneous characteristics of the urban expansion process is essential for understanding the dynamics of the urban spatial structure. Many studies focused on depicting the spatio-temporal characteristics based on urban expansion patches. However, measuring heterogeneous characteristics of urban expansion from agglomeration areas comprising the expanded urban construction land patches have not been adequately explored. This study presents a novel approach and two improved indices for characterizing the heterogeneity of urban spatial agglomeration areas during urban expansion. Firstly, we proposed a Gaussian mixture model considering multiple constrains and density-based spatial clustering of applications with noise (DBSCAN) integration method to identify and extract the urban agglomeration areas automatically. Secondly, the gradient analysis and the compact index using the inverse “S” function are introduced to explore the spatio-temporal characteristics from a macrocosmic perspective. Finally, the compactness index (NCI) and normalized dispersion index (NDIS) are improved based on agglomeration area data. The microcosmic heterogeneous characteristics are measured by these two improved indices and the positional offset characteristics indices (POCIS). The method was implemented in the urban area of Changsha, Hunan Province, China in 2005, 2010, and 2015. The results show that (1) compared to that in the Changsha City Master Plan (2003–2020), the recognition rate was higher in the agglomeration areas than others. (2) The overall expansion trend in Changsha transitioned toward decentralization, making Changsha a polycentric city. (3) The agglomeration of urban expansion in the east-west direction became compact; that in the north-south direction became looser; most clusters expanded to the west and a new sub-center would appear. The proposed method can effectively characterize their heterogeneity, which can provide valuable references for urban planning and policymaking.