Sea lamprey, Petromyzon marinus, are an invasive species in the Laurentian Great Lakes and Finger Lakes. The parasitic feeding stage is particularly damaging to the lakes’ ecosystem as sea lamprey wound and kill environmentally and economically important fish such as lake trout, Salvelinus namaycush. Since the sea lamprey invasion in the late 1800s significant resources are directed towards the control of sea lamprey using tools such as chemical treatment of larvae and trapping of the spawning adults. Understanding population structure is essential for framing a more effective sea lamprey control program. Studies using microsatellite loci have found genetic differentiation between sea lamprey from the upper and lower Great Lakes, and body size variation has been documented across the lakes, but fine-scale genetic population structure has not been studied. We use whole genome resequencing of 9-20 individuals from each of 15 sites (238 individuals) across the Great Lakes and Finger Lakes (Cayuga and Seneca), and body measurements of 9-36 individuals from each site (472 individuals), to identify population structure among and within the lakes. Genomic analyses showed structure between Lake Ontario, the Finger Lakes, and the other Great Lakes, and body size partially differentiated the lakes. Using high-resolution data to delineate spatial population structure will be important for sea lamprey control because management is most efficiently targeted when the geography of demographically independent populations is well-characterized.