With accelerating globalization and urbanization, population mobility has profoundly reshaped the social spatial structures of cities. Spatial differentiation of employment among social groups not only reflects the degree of social integration but also has direct implications for the formulation of inclusive urban policies. However, existing studies have largely focused on residential spatial differentiation, while the spatial differentiation of employment and its formation mechanisms remain insufficiently examined in a systematic manner. Based on mobile phone signaling data, this study takes Hangzhou, a rapidly developing megacity in China, as a case to investigate the characteristics of employment spatial differentiation between migrants and local residents. A Multiscale Geographically Weighted Regression (MGWR) model is then employed to investigate the mechanisms underlying these patterns. The results show that Hangzhou has become a migrant-dominated city, where migrants and local residents exhibit a relatively high degree of integration in employment space. Employment among local residents is primarily concentrated in the old urban areas, whereas migrants’ employment is more dispersed across peripheral areas, forming a polycentric pattern along major transportation corridors. Overall, the employment spatial structure can be characterized as a composite pattern of polycentric, sector-shaped, and concentric-ring structures. The findings further indicate that employment spatial differentiation is mainly shaped by commercial facilities and housing prices, and is also influenced by urban spatial expansion and migrants’ sectoral employment choices. By shedding light on the social spatial characteristics of population-dense and migration-intensive regions, this study provides new empirical evidence for understanding urban social space and offers policy-relevant insights for fostering inclusivity through spatial planning and development guidance.