The adoption of grain amaranth (Amaranthus hypochondriacus L.) as a climate-smart crop due to its hardiness and drought escape mechanisms in sub-Saharan Africa is under threat from the lack of pure seed due to contamination by weedy relatives, such as pigweed (A. hybridus L.). Due to limited land availability, proper isolation distances to attain seed purity in the small-scale farming sector are impossible. A study investigating the cross-pollination rate between grain amaranth and pigweed at distances between 3 and 150 m was conducted at three sites in Zimbabwe during the 2020/2021 and 2021/2022 rainy seasons. Grain amaranth was planted at radial distances of 3 to 150 m from the pure pigweed plot. Meteorological conditions, such as temperature and wind speed and direction, were measured during the anthesis period. The cross-pollination rate in grain amaranth was influenced by distance from the pollen source. A maximum cross-pollination rate of 12.9% was observed within a 10 m radius from the pollen donor plot, and a minimum outcrossing rate of 0.45% was recorded at 150 m. The complete removal of weedy relatives within an extrapolated distance of 325 m is recommended to maintain the genetic purity of grain amaranth in small-scale farming systems.