We employed direct numerical simulations to estimate the error on chemical calculation in simulations with regional chemical-transport models induced by neglecting subgrid chemical segregation due to inefficient turbulent mixing in an urban boundary layer with strong and heterogeneously distributed surface emissions. In simulations of initially segregated reactive species with an entrainment-emission configuration with an A-B-C second-order chemical scheme, urban surface emission fluxes of the homogeneously emitted tracer A result in a very large segregation between the tracers and hence a very large overestimation of the effective chemical reaction rate in a complete-mixing model. This large effect can be indicated by a large Damköhler number (Da) of the limiting reactant. With heterogeneous surface emissions of the two reactants, the resultant normalised boundary-layer-averaged effective chemical reaction rate is found to be in a Gaussian function of Da, and it is increasingly overestimated by the imposed rate with an increased horizontal scale of emission heterogeneity. Coarse-grid models with resolutions commensurable to regional models give reduced yet still significant errors for all simulations with homogeneous emissions. Such model improvement is more sensitive to the increased vertical resolution. However, such improvement cannot be seen for simulations with heterogeneous emissions when the horizontal resolution of the model cannot resolve emission heterogeneity. This work highlights particular conditions in which the ability to resolve chemical segregation is especially important when modelling urban environments.