Cities host most of the world's population with diverse services and activities. One key challenge in urban modelling is the quantification of intra- and inter-city mobility patterns and the associated space–time dynamics of population density and anthropogenic activities. To address this, we apply the novel agent-based urban model DAVE (Dynamic Anthropogenic actiVities and feedback to Emissions) to simulate population behaviour and mobility in the Vaud and Geneva Cantons, a system of small- to medium-size cities in Switzerland. Simulation results provide detailed temporal (10 min) and spatial (500 m) population dynamics for different age groups and day types. DAVE further models the time-varying population distribution in 11 different microenvironments (e.g. home, work, leisure, outdoor) and the travel flows by different modes. Simulation results align with observations, confirming the possibility of driving urban system modelling with statistical information on residents’ behaviour. Sustainability and health indicators like daily driving distance and walking time for each neighbourhood are also reflected by the model with urban–rural gradients displayed. This work serves as a foundation for future applications of DAVE to study bottom-up human-built environment interactions, from anthropogenic emissions and building energy to urban climate, exposure and health in cities around the world.