As of 2023, 188 non-native species have been identified in the Laurentian Great Lakes, with about half being considered benign. Some of these species have been elevated to the status of invasive (i.e. causing extreme negative effects). Here, we identified and quantitatively ranked in order of impact (highest to lowest), the top ten aquatic nonindigenous species (ANS) determined to have the most significant negative environmental and socio-economic effects. To accomplish this, we used an organism impact assessment (OIA) tool developed by the Great Lakes Aquatic Nonindigenous Species Information System (GLANSIS). The top ten identified species included: zebra mussel (Dreissena polymorpha); quagga mussel (Dreissena bugensis); alewife (Alosa pseudoharengus); sea lamprey (Petromyzon marinus); Japanese stiltgrass (Microstegium vimineum); grass carp (Ctenopharyngodon idella); water chestnut (Trapa natans); common reed (Phragmites australis australis); round goby (Neogobius melanostomus); and white perch (Morone americana). The taxonomic groupings, continent of origin, and vectors of introduction of these top ten invaders do not reflect the full diversity of all invasive species in the Great Lakes region. The most common shared negative effects were: direct hazards or threats posed to native species, alteration of predator/prey dynamics, aggressive competition with native species, and costly damage to human recreation, aesthetics, and economic activities. These quantitative rankings of the top ten most harmful ANS can serve as a reference point for researchers, educators and communicators as the Great Lakes continue to be affected by the spread of invasive species and other contemporary and future anthropogenic factors affecting the Great Lakes ecosystem.