Riparian areas experience strong invasion pressures worldwide and represent important points of spread for invasive alien plants (IAPs) in the European mainland. The Danube Basin is a well-known point of high plant invasion levels. Given that the middle part of the Danube Basin is critically understudied and the general lack of data for Serbia, the study aimed to provide an insight into the spatial patterns of plant invasions in the riparian areas of Serbia (Middle Danube Basin area). A total of 250 field sites, distributed along 39 rivers (nine catchment areas) and six canal sections, were studied during a four-year period (2013–2016) for the presence and abundance of IAPs. At the landscape scale, we studied distribution patterns of IAPs, differences in invasion levels in different catchment areas and between rivers and canals. At the local scale, we investigated how the proximity to roads/railway lines, housing areas, different land-use types (primarily agriculture), and dominant vegetation on site related to invasion patterns. Of the 26 studied IAPs, those with a well-known weedy behavior, long history of cultivation and strong affinity for riparian areas prevailed in the study area. Riparian zones of the Danube catchment exhibited the highest invasion levels in terms of IAPs richness and abundance, followed by the catchment areas of the Timok, Sava and Zapadna Morava rivers. Surprisingly, the Danube-Tisa-Danube canal network had the lowest invasion level. At the local scale, agriculture in proximity of the field site and dominant vegetation on site were observed as significant predictors of the invasion level. On the other hand, proximity to roads/railway lines and housing areas was not related to the invasion level. Finally, our study provides the first systematic overview of IAPs’ distribution data for riparian areas of the Middle Danube Basin in Serbia, which could provide a basis for long-term monitoring of IAPs and development of future management plans.