Background: Invasive species are a major threat to biodiversity, human health, and economies worldwide. The cost of the damages and the fight against them exceeds 9.6–12.7 billion euros annually for European Union. The Pannonic open sand grasslands represent important endemic habitats in European Union and are threatened by the spread of several invasive plant species. Among them, the common milkweed Asclepias syriaca L. has already transformed large areas of natural vegetation and endangered the others. The need for management of alien plants is urgent in both agricultural and protected areas. Herbicide treatment may be a cost-effective method for controlling the extended stand of milkweed even in protected areas. Therefore, this study monitored the herbicide treatment effects on A. syriaca before, during, and after treatment in a strictly protected UNESCO biosphere reserve near Fülöpháza from 2011 to 2017. The entire stand was treated with glyphosate in May 2014. We used simple data processing methods to follow the fate of individual shoots. Results: The 7-year data showed that treatment was successful for a short term (the year of treatment and the following year). The number of A. syriaca shoots in the stand decreased following herbicide treatment, with 73% of the shoots dying. In the first year after treatment, the number of shoots decreased continuously as herbicides were translocated by rhizomatic roots, thereby damaging dormant bud banks. Conclusions: The surviving buds adjusted to the number of emerging shoots in the years after treatment, and growth of the milkweed stand appeared to show a slow regeneration for a longer-term period. We concluded that the successful control of A. syriaca after herbicide treatment depends on continuous management (e.g., further point spraying) of treated areas to suppress possible regrowth during subsequent seasons. Therefore, periodic control is highly recommended because one-time treatment is insufficient.