Detection and mapping of Sosnowsky’s hogweed (HS) using remote sensing data have proven effective, yet challenges remain in identifying, localizing, and eliminating HS in urban districts and regions. Reliable data on HS growth areas are essential for monitoring, eradication, and control measures. Satellite data alone are insufficient for mapping the dynamics of HS distribution. Unmanned aerial vehicles (UAVs) with high-resolution spatial data offer a promising solution for HS detection and mapping. This study aimed to develop a method for detecting and mapping HS growth areas using a proposed algorithm for thematic processing of multispectral aerial imagery data. Multispectral data were collected using a DJI Matrice 200 v2 UAV (Dajiang Innovation Technology Co., Shenzhen, China) and a MicaSense Altum multispectral camera (MicaSense Inc., Seattle, WA, USA). Between 2020 and 2022, 146 sites in the Moscow region of the Russian Federation, covering 304,631 hectares, were monitored. Digital maps of all sites were created, including 19 digital maps (orthophoto, 5 spectral maps, and 13 vegetation indices) for four experimental sites. The collected samples included 1080 points categorized into HS, grass cover, and trees. Student’s t-test showed significant differences in vegetation indices between HS, grass, and trees. A method was developed to determine and map HS-growing areas using the selected vegetation indices NDVI > 0.3, MCARI > 0.76, user index BS1 > 0.10, and spectral channel green > 0.14. This algorithm detected HS in an area of 146.664 hectares. This method can be used to monitor and map the dynamics of HS distribution in the central region of the Russian Federation and to plan the required volume of pesticides for its eradication.