Anthropogenic modification of natural landscapes to urban environments impacts land-atmosphere interactions in the boundary layer. Ample research has demonstrated the effect of such landscape transitions on development of the near-surface urban heat island (UHI), while considerably less attention has been given to impacts on regional wind flow. Here we use a set of high-resolution (1 km grid-spacing) regional climate modeling simulations with the Weather Research and Forecasting (WRF) model coupled to a multi-layer urban canopy scheme to investigate the dynamical interaction between the urban boundary layer (UBL) of the Phoenix Metro (U.S.) area and the thermal circulation of the complex terrain it resides within. We conduct paired simulations for the extremely hot and dry summer of 2020, using a contemporary urban representation and a pre-settlement landscape representation to examine the effect of the built environment on local to regional scale wind flow. Analysis of our simulation results shows that, for a majority of the diurnal cycle, 1) the thermo-topographical circulation dominates, 2) the built environment obstructs wind flow in the inertial sublayer during the nighttime, and (3) the built environment of Phoenix Metro produces an UHI circulation of limited vertical extent that interacts with the background flow to modulate its intensity. Such interaction is modulated by greater daytime urban sensible heat flux and dampens the urban roughness induced drag effect by promoting a deeper UBL through vigorous mixing. Our results highlight the need for future research – both observational and simulation based - into urbanizing regions where multi-scale flows are dominant.