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 urban heat island (UHI), but 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 model coupled to a multilayer urban canopy scheme to investigate the dynamical interaction between the urban boundary layer of the Phoenix metro (United States) 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, during the summer of 2020, (a) the thermo-topographical circulation dominates over both urban and rural areas for a majority of the diurnal cycle; (b) the built environment obstructs wind flow in the inertial sublayer during the late afternoon and the nighttime, whereas more intense daytime urban sensible heat flux dampens the urban-roughness-induced drag effect through a deeper urban boundary layer and vigorous mixing; (c) the Phoenix metro UHI does not result in a well-developed and clearly discernible induced circulation as observed in other urban areas and described in the scientific literature; (d) shortly before dawn, the local UHI is able to affect the local thermo-topographical circulation through flow intensity modulation that results in an similar to 10 km eastward shift of the center of mass convergence. Our results highlight the need for future research-both observational and simulation based-into urbanizing regions where multiscale flows are dominant.