Artificial levees are a major human modification of river corridors, but we still do not have a clear understanding of how artificial levees affect floodplain extent at regional and larger scales. We estimated changes in river-floodplain connectivity due to artificial levees in the contiguous United States (CONUS) using a combination of artificial levee databases, delineations of floodplain areas, and deletion of artificial levees from topography. Our results indicate that artificial levees do not only decrease floodplain extent but also alter locations of floodplain connectivity. Anthropogenically connected and disconnected locations are similar in land cover and are predominantly, in decreasing order of extent, cultivated, wetland, forested, and developed land cover types, with more than 30% of the entire floodplain area in the CONUS cultivated or developed. This study indicates that artificial levees cause complex changes in river-floodplain connectivity and can increase flooded areas in some rivers.