We postulated that dispersal through streams is an important factor in the spread of nonindigenous aquatic species to uninvaded lakes. We tested this hypothesis with zebra mussels (Dreissena polymorpha), whose planktonic larvae are particularly prone to transport through streams. To examine this potential mechanism of spread, we (1) assessed populations of zebra mussels in 2000 and 2003 in coupled lake-stream systems of the St. Joseph River basin (Indiana and Michigan, USA) and (2) examined the interconnectedness of lake-stream systems by evaluating all invaded inland lakes and reservoirs in the United States. We compared observed patterns in zebra mussel populations in 2000 and 2003 to patterns predicted by two proposed models of spread: the static source–sink model and the progressive downstream-march model. Adult zebra mussel densities in lake outflows declined with distance downstream of invaded lakes. Maximum downstream occurrences of adults were variable over the years surveyed, but did not increase through time, suggesting that the source–sink model best fit zebra mussel distributions in these lake-stream couplets. For the conterminous US, we examined the connectedness of inland lakes in close proximity to invaded lakes to determine if stream connections were related to invasions. We also measured the distances between invaded lakes and downstream lakes that were potential recipients of colonists to examine the importance of stream distance in relation to zebra mussel invasions. Lakes connected to invaded lakes were more likely to be invaded than non-connected lakes, and the probability of becoming invaded increased with the proximity between lakes. Our results suggest that a better understanding of the role that streams play as pathways for new biological invasions is crucial for directing management and prevention efforts.