Zebra mussels (Dreissena polymorpha) have continued their spread within inland lakes and rivers in North America despite diligent containment and decontamination efforts by natural resource agencies and other stakeholders. Identification of newly infested waterways with early detection surveillance programs allows for rapid response zebra mussel eradication treatments in some situations. Previous eradication treatments have been conducted during times of variable water temperatures and temperature has been shown to influence the efficacy of molluscicides. Natural resource managers would benefit from knowledge regarding the impacts of water temperature and exposure duration on toxicity of molluscicides to zebra mussels. In particular, temperature specific data are needed to inform the selection of an effective molluscicide and the proper dose that will induce 100% zebra mussel mortality. We evaluated the influences of temperature and exposure duration on the toxicity of two EPA-registered (EarthTec QZ and Zequanox) and two nonregistered (niclosamide and potassium chloride) molluscicides to zebra mussels at water temperatures of 7, 12, 17, and 22 °C. Our results indicate that treatment options for the eradication of zebra mussels in waters ≤ 12 °C include 336 h or longer treatments with EarthTec QZ and KCl and treatments with niclosamide ≥ 24 h in duration. In waters ≥ 17 °C, multiple toxicant and exposure duration combinations would be effective for zebra mussel eradication treatments. However, site specific variables should be considered prior to treatment including: the extent of the infestation, water chemistry, aquatic vegetation, substrate, and the presence of nontarget organisms. The use of on-site or in situ zebra mussel bioassays would also be a useful tool for the evaluation of treatment efficacy. The dataset includes: Water Quality, Chemical Concentrations, Mortality, and Zebra Mussel Condition Data