The dynamics of zoonotic vector-borne diseases are determined by a complex set of parameters including human behavior that may vary with socio-ecological contexts. Lyme disease is the most common vector-borne disease in the United States and the Northeast and upper Midwest are the regions most affected - two areas with differing levels of urbanization and sociocultural settings. The probability of being diagnosed with Lyme disease is related to the risk of encounters with an infected blacklegged tick, which reflects both the environmental tick hazard and human behaviors. Herein, we compare behavioral and peridomestic risk factors associated with human-tick encounters between high-incidence states in the Northeast (New York and New Jersey) and Midwest (Wisconsin) of the United States. We used a smartphone application, The Tick App, as a novel survey tool, during spring and summer of 2018. Adaptive human behavior was identified in the relationship between outdoor activities and the use of preventive methods. More frequent recreational outdoor activities and gardening (a peridomestic activity) were associated with an increased likelihood of using personal protective measures. Weekly participation in non-seasonal recreational and peridomestic outdoor activities in spring and summer was associated with an increased likelihood of finding a tick in the fall or winter. Most outdoor activities were more frequently reported by participants from the Midwest than the Northeast. Participants in the Northeast reported less use of personal protective measures, but they reported more interventions to reduce the presence of peridomestic deer and ticks (i.e. pesticide applications on their property) than participants in the Midwest. Participants from the Midwest were more likely to kill rodents on their property. Context mattered, and our study illustrates the need for the assessment of personal behavior and tick exposure in these two Lyme disease-endemic regions to aid in targeted public health messaging to reduce tick-borne diseases.