Landscape composition and structure may strongly affect the spread of invasive species in landscapes. Landscape analysis provides a powerful toolset for assessing invasive species invasions over time and for planning control measures. We applied a combination of aerial mapping and landscape analysis to assess the invasion of the legume, Lupinus polyphyllus, in the Rhön UNESCO Biosphere Reserve. The Biosphere Reserve contains different types of large and well-connected grasslands threatened by lupine invasion. We assessed the changes in lupine distribution between 1998 and 2016 in a strictly protected part of the Biosphere Reserve by means of landscape structure analysis. The area invaded by L. polyphyllus doubled from 1998 to 2016. While the number of lupine stands decreased by 25%, stand size on average increased by 300%; stands also became less compact during that period. Furthermore, the degree of invasion of different grassland types changed. In 1998, all investigated grassland types were invaded to equal extents, whereas in 2016, large and well-connected mesic grasslands located close to roads were more heavily invaded than small and remote wet grasslands. Our results show that landscape composition plays an important role for the spread of lupine. Specifically, invasive stand characteristics, such as stand size, form, and connectivity, are crucial for driving the invasion of lupine. Therefore, in addition to landscape composition, invasive stand characteristics should be included in the planning of conservation measures. Overall, aerial mapping combined with landscape analysis provides a cost-effective and practical tool for landscape managers to prioritize invasive control measures.