Lyme disease transmission dynamics in the northeastern United States vary by context. Periurban regions, including Block Island, RI, have experienced decades of endemic transmission. In urban areas, including Staten Island, a borough in New York City, NY, Lyme disease is an emerging issue. Knowledge, attitudes, and practices around Lyme disease evolve as an area progresses from emergent to endemic. We conducted focus group discussions and household surveys within Staten Island, NY and Block Island, RI to compare knowledge, attitudes, and practices surrounding Lyme disease and other tick-borne diseases. Qualitative data were coded into themes, and survey data were used to provide more general context of the focus group discussions. Using item response theory, we developed an index of knowledge from relevant factors within the household survey. We identified a significant difference in knowledge scores between the two study areas. Additionally, we identified key differences across multiple domains. Participants from Block Island were more likely to report prior tick exposure and Lyme disease in themselves or household members and were more likely to express concerns about the environmental impact of mitigation strategies. Individuals on Staten Island were more likely to assign responsibility of prevention and control to local, state, and federal government than to take personal prevention measures. Prevention of Lyme disease and other tick-borne diseases must be tailored to the community context and monitored over time as perceptions and priorities may evolve as transmission dynamics transition from emergent to endemic.