Computational fluid dynamics (CFD) simulations and wind-tunnel (WT) tests can be considered as boundary-value problems, where the inlet boundary condition, which is usually obtained inferring inlet mean wind profiles from on-site measurements or other type of experimental data, represents the large-scale atmospheric forcing exerted at the outer limit of the urban model. It is not clear, however, to which extent the choice of different inflow wind speed profiles may affect WT and CFD results in the urban environment. In the present study, this aspect is investigated through the comparison of the wind flow fields simulated numerically and tested experimentally in an atmospheric boundary layer wind tunnel (ABLWT) within a district of Livorno city, Italy, called “Quartiere La Venezia”. Three different shapes of inflow profiles were tested using the CFD technique and the results were compared with each other: one is based on the approach-flow profiles measured upstream of the urban model in the WT test section (WT profile) and two are based on anemometric data corresponding to the approach-flow profile measured by means of a LiDAR wind profiler (LiDAR profile 1 and 2). The analysis showed that using different wind speed profiles does not affect significantly the results in the urban canopy layer (UCL), where correlations of 95% and 98% were found between the LiDAR profile 1 and 2 data and the WT profile data (at z = 0.02 m above the bottom), respectively. Conversely, the different inflow profiles strongly affected the results above the UCL. This means that the local-scale effects induced on the wind field in the UCL by the urban texture are dominated mainly by the larger-scale forcing, as within the canopy the flow remains topologically invariant despite the different inflow conditions.