Urbanization is a long-term global trend critical for shaping human-Earth sustainability in the Anthropocene. In past decades, much progress has been made in researching urban sustainability, particularly global assessments of the big picture and case studies of individual cities. Here we examine the world's top 100 urban agglomerations (UAs) in terms of size—that rank high on sustainability agendas and cover 28% of the global UA area—regarding four broadly concerned challenges: population shrinkage, slum development, greenness loss, and heat exposure. Instead of merely focusing on global/regional “averages” or individual cases, we take one step further to identify the “anomalies” of urban sustainability among the 100 UAs for each dimension and on the whole as multi-dimensional coupled infrastructure systems. Results show: (1) urban population of the 100 UAs increased by 36% during 2000–2020; (2) urban slums occurred in 85% of 34 examined UAs in the Global South; (3) urban greenness declined in the 100 UAs by 8% during 2000–2019; and (4) 79% of the 100 UAs were projected to have less than 30 EHDs per year during 2021–2030. Our findings provide global baselines for place-based problem-driven policymaking for the examined UAs and suggest improving urban green infrastructure as their top policy imperative. Our findings point to a critical research gap in the urban sustainability literature: Studying sustainability transitions of the “abnormally” sustainable UAs identified in this study that had exceptional performances on the four examined sustainability dimensions, e.g., Beijing of China and Milan of Italy.