An Environmental Justice (EJ) analysis was carried out using full Chemical Transport Models (CTMs) over Los Angeles, California, to determine how the combination of domain size and spatial resolution affects predicted air pollution disparities in present day and future simulations when data support from measurements is not available. One set of simulations used the Weather Research and Forecasting (WRF) model coupled with Chemistry (WRF/Chem) with spatial resolution ranging from 250 m to 36 km, comparable to census tract sizes, over domains ranging in size from 320 km2 to 10,000 km2. A second set of simulations used the UCD/CIT CTM with spatial resolution ranging from 4 km to 24 km over domains ranging in size from 98,000 km2 to 1,000,000 km2. Overall WRF/Chem model accuracy improved approximately 9% as spatial resolution increased from 4 km to 250 m in present-day simulations, with similar results expected for future simulations. Exposure disparity results are consistent with previous findings: the average Non-Hispanic White person in the study domain experiences PM2.5 mass concentrations 6–14% lower than the average resident, while the average Black and African American person experiences PM2.5 mass concentrations that are 3–22% higher than the average resident. Predicted exposure disparities were a function of the model configuration. Increasing the spatial resolution finer than approximately 1 km produced diminishing returns because the increased spatial resolution came at the expense of reduced domain size in order to maintain reasonable computational burden. Increasing domain size to capture regional trends, such as wealthier populations living in coastal areas, identified larger exposure disparities but the benefits were limited. CTM configurations that use spatial resolution/domain size of 1 km/103 km2 and 4 km/104 km2 over Los Angeles can detect a 0.5 μg m−3 exposure difference with statistical power greater than 90%. These configurations represent a balanced approach between statistical power, sensitivity across socio-economic groups, and computational burden when predicting current and future air pollution exposure disparities in Los Angeles.