Zebra (Dreissena polymorpha) and quagga mussels (Dreissena rostriformis bugensis) first invaded the North American Great Lakes via ballast water discharge in the mid-1980’s. While zebra mussels have spread throughout most inland rivers and lakes in the Eastern United States, quagga mussels expanded into the western U.S. in the early 2000’s, establishing in cooler inland lakes and rivers from Colorado to California. Understanding genetic and morphological differences across quagga mussel populations is crucial for deciphering invasion pathways. Our objective was to determine genetics, morphology, and physiological responses to cyanobacteria in populations from an earlier Detroit River invasion and the more recent Lake Mohave invasion. We assessed mussel spawning, filtration rates, oxidative stress, and shell traits between the two populations. Sequencing results showed no taxonomic differences between the two populations, though morphological differences were evident for shell shape and size. Lake Mohave mussels had longer and taller shell shapes, while Detroit River mussels had heavier and wider shells. Reproductive responses were similar between the two populations, both showing decreased spawning when exposed to Microcystis icthyoblabe. However, filtration rates and oxidative stress differed between the two locations. Lake Mohave mussels exhibited a decrease in filtration over time, while Detroit River mussels initially filtered slowly but increased filtration after prolonged exposure. These phenotypic and physiological changes suggest that quagga mussels can rapidly adapt to local conditions within 20 years of invasion.