Urbanization substantially changes the physicochemical and biological characteristics of streams. The trajectory of negative effect is broadly similar around the world, but the nature and magnitude of ecological responses to urban growth differ among locations. Some heterogeneity in response arises from differences in the level of urban development and attributes of urban water management. However, the heterogeneity also may arise from variation in hydrologic, biological, and physicochemical templates that shaped stream ecosystems before urban development. We present a framework to develop hypotheses that predict how natural watershed and channel attributes in the pre-urban-development state may confer ecological resistance to urbanization. We present 6 testable hypotheses that explore the expression of such attributes under our framework: 1) greater water storage capacity mitigates hydrologic regime shifts, 2) coarse substrates and a balance between erosive forces and sediment supply buffer morphological changes, 3) naturally high ionic concentrations and pH pre-adapt biota to water-quality stress, 4) metapopulation connectivity results in retention of species richness, 5) high functional redundancy buffers trophic function from species loss, and 6) landuse history mutes or reverses the expected trajectory of eutrophication. Data from past comparative analyses support these hypotheses, but rigorous testing will require targeted investigations that account for confounding or interacting factors, such as diversity in urban infrastructure attributes. Improved understanding of the susceptibility or resistance of stream ecosystems could substantially strengthen conservation, management, and monitoring efforts in urban streams. We hope that these preliminary, conceptual hypotheses will encourage others to explore these ideas further and generate additional explanations for the heterogeneity observed in urban streams.