In the conditions of a high urbanization level in the modern world, the quality of urban environment is the most important element of living standards. The purpose of the research is to develop and test a methodology for index assessment of the territorial differentiation of the quality of megalopolis environment. The scientific novelty of the study consists in a micro-detailed analysis of the functional saturation of the urban environment: each urban microdistrict is considered from the point of view of performing residential, labor, recreational and leisure functions. The methodology, developed by the authors, is based on the theoretical basis of modern urban ideas (multifunctionality of urban areas, polycentricity of urban development, walking distance of key urban services and goods) and instrumental platform of the index method, which allows integrating a large array of data characterizing various aspects of urban life. We have carried out the approbation of the methodology in the case of studying 66 microdistricts of Yekaterinburg. The empirical basis for calculating the environmental quality indices of urban microdistricts is data of official municipal statistics and population survey results. The conducted research proved the following: 1) the formation of polycentricity of a non-industrial type: strengthening the leadership positions of service-oriented microdistricts and reducing the attractiveness of the largest microdistricts of the industrial development period of Yekaterinburg; 2) high differentiation of microdistricts both by individual environmental components and by functional indices when the maximum index values are not reached even by the leading microdistricts; 3) problems of implementing a multifunctional development model for a significant number of urban microdistricts and population living in them; 4) differences between objective and subjective assessments of the quality of urban environment indicating a dissonance in the system of “converting” formal statistical indicators into living standards and well-being of residents. The results are practically useful to develop priority areas for improving the environment quality at the level of urban neighborhoods.