Abstract: Herbicide selection is key to efficiently managing nuisance vegetation in our nation’s waterways. After selecting the active ingredient, there still remains multiple proprietary and generic products to choose from. Recent small-scale research has been conducted to compare the efficacy of these herbicides against floating and emergent species. Therefore, a series of mesocosm and growth chamber trials were conducted to evaluate subsurface applications of the following herbicides against submersed plants: diquat versus coontail (Ceratophyllum demersum L.), hydrilla (Hydrilla verticillata L.f. Royle), southern naiad (Najas guadalupensis (Sprengel) Magnus), and Eurasian watermilfoil (Myriophyllum spicatum L.); flumioxazin versus coontail, hydrilla, and Eurasian watermilfoil; and triclopyr against Eurasian watermilfoil. All active ingredients were applied at concentrations commonly used to manage these species in public waters. Visually, all herbicides within a particular active ingredient performed similarly with regard to the onset and severity of injury symptoms throughout the trials. All trials, except diquat versus Eurasian watermilfoil, resulted in no differences in efficacy among the 14 proprietary and generic herbicides tested, and all herbicides provided 43%–100% control, regardless of active ingredient and trial. Under mesocosm and growth chamber conditions, the majority of the generic and proprietary herbicides evaluated against submersed plants provided similar control.