Abstract Background Lyme disease is the most common reportable zoonotic infection in the United States. Recent data suggest spread of the Ixodes tick vector and increasing incidence of Lyme disease in several states, including Pennsylvania. We sought to determine the clinical presentation and healthcare use patterns for pediatric Lyme disease in western Pennsylvania. Methods The electronic medical records of all patients with an International Classification of Disease, Ninth Revision, diagnosis of Lyme disease between 2003 and 2013 at Children's Hospital of Pittsburgh were individually reviewed to identify confirmed cases of Lyme disease. The records of 773 patients meeting these criteria were retrospectively analyzed for patient demographics, disease manifestations, and healthcare use. Results An Lyme disease increased exponentially in the pediatric population of western Pennsylvania. There was a southwestward migration of Lyme disease cases, with a shift from rural to nonrural zip codes. Healthcare provider involvement evolved from subspecialists to primary care pediatricians and emergency departments (EDs). Patients from nonrural zip codes more commonly presented to the ED, while patients from rural zip codes used primary care pediatricians and EDs equally. Conclusions The current study details the conversion of western Pennsylvania from a Lyme-naive to a Lyme-epidemic area, highlighting changes in clinical presentation and healthcare use over time. Presenting symptoms and provider type differed between those from rural and nonrural zip codes. By elucidating the temporospatial epidemiology and healthcare use for pediatric Lyme disease, the current study may inform public health measures regionally while serving as an archetype for other areas at-risk for Lyme disease epidemics. We identified 773 children with Lyme disease in western Pennsylvania, a previously Lyme-naive region. Over 10 years, the number of cases increased exponentially, with the highest burden of infection shifting from rural to nonrural areas and affecting healthcare use.