In a global context of increasing flexibility in the way workplaces and the districts in which they are located are used, there is a need for occupant-driven approaches to plan urban energy systems. Several authors have suggested the use of agent-based models (ABM) of building occupants in urban building energy simulations due to their ability to reproduce emergent behaviors from individual agents’ actions. However, few works in the literature take full advantage of the ABM paradigm, accounting for both occupant presence and energy-relevant behaviors at the district scale. In this work, we propose a methodology to develop a data-driven, agent-based model of building occupants’ activities and thermal comfort in an urban district. Our methodology combines the use of campus-scale Wi-Fi data to derive feasible occupant activity and location plans, along with thermal preference profiles derived from a longitudinal field study where off-the-shelf, non-intrusive sensors were used to capture the right-here-right-now thermal preference of 35 participants in the same case study district. Our model is then used to explore how different district operation strategies could affect building energy performance in the context of increased workspace flexibility. Our results show that by providing a diversity of building operation conditions, with different buildings having different set point temperatures, occupants’ thermal comfort hours could be improved by an average of about 10% with little effect on district energy performance. Meanwhile, a 6%–15% average decrease in space cooling energy use intensity was observed when implementing occupant-driven ventilation and setpoint controls, regardless of location choice scenario. ; Environmental & Climate Design