Invasive species can have severe effects on aquatic ecosystems. After invasions occur, eradication should be considered whenever the potential loss of ecosystem services outweighs the cost of the eradication method. Here we evaluate the possibility of destratifying Crystal Lake, Wisconsin, USA, to eradicate the invasive fish rainbow smelt (Osmerus mordax). We modeled the effects of three destratification scenarios (non-, low-, and high-mixing) using both physical and biological models. Field observations were used to calibrate the models. Water temperatures estimated from 18 unique DYRESM simulations were used in a bioenergetics model to estimate growth of five age classes of rainbow smelt under normal and destratified conditions. Our simulations indicate that destratification can eliminate optimal rainbow smelt thermal habitat resulting in mortality. Destratified lake temperatures also surpassed several physiological critical temperatures. Bioenergetics simulations predicted a weight loss of 45–55% in yearling and adult rainbow smelt. We found that destratification is potentially effective for eradicating cold-water species in temperate lakes.