Horseweed (Conyza canadensis) with evolved herbicide resistance has become an especially problematic weed in crop production across the United States and on four continents. Resistant horseweed biotypes can pollinate susceptible horseweed to facilitate the spread of herbicide resistance through gene flow. Although horseweed pollen dispersal is wind-borne, there is little knowledge, preventive guidelines, and mechanism modeling for pollination gene flow in this system. We need to better understand pollen dispersion, deposition, and outcrossing in the context of atmospheric conditions, herbicide-resistant horseweed patch size, pollen size, buffer crop type, height, and field size. A pollen dispersion and deposition model was calibrated and validated using 2013 experimental field data. The average model error for the simulation of pollen concentration was -1% and the error for the simulation of pollen deposition was 29%. The validated model was run for various combinations of atmospheric conditions, horseweed characteristics, and buffer species and size. Large fields with crops with a high leaf area density and tall plants can effectively prevent pollen dispersion. The information will help provide guidelines for preventing herbicide-resistance spread/gene flow from herbicide-resistant weeds and genetically modified plants in general.