The evolution of cities is important for tracing a hydrological vision of territories and their sustainability, as urban morphologies and uses regulate inflow-outflow processes. The analysis of water flows in urban areas under different conditions allows us to evaluate the hydrological response, the hydromorphic characteristics and their interrelation with urban, architectural or administrative characteristics. This study presents an approach for the hydromorphic analysis of changes in urban basins and evaluation of the hydrological response applied to the city of Matera (Italy). Matera—in particular the Sassi—is an ideal case study: over time, it has evolved as a complex urban ecosystem of homes and water infrastructures for collection, storage and drainage, while in recent years the transformation of the city has led to frequent urban pluvial flooding events. The study adopted several two-dimensional models for hydrodynamic simulations: an adapted version of FLO-RA-2D and LISFLOOD-FP with three numerical schemes (Acceleration, Flow-Limited and Roe). The analysis of two urbanization scenarios (1954 and 2019) allowed us to identify the urban areas most subject to flood phenomena, coinciding with the road network and the downstream areas.