Studies show that telestroke (TS) improves rural access to care and outcome for stroke patients receiving TS services, but population health impacts of TS are not known. We examine impacts associated with South Carolina's (SC) statewide TS network on an entire state population of patients suffering acute ischemic stroke (AIS) as TS became available across SC counties. A population health study using Donabedian's conceptual model and an ecological design to describe the change observed over time in use of thrombolysis and endovascular therapy (EVT) as the SC TeleStroke Network (SCTN) diffused across SC counties. Changes in county rates of stroke mortality and discharge destination are reported. The unit of interest is the population rate for AIS patients living in a SC county. Patients' county of residence at the time of hospitalization defined county cohorts. Relative risks were estimated using logistic regression adjusted for age >75 years. Overall tissue plasminogen activator (tPA) rate was 6.28%, and EVT rate was 1.10%. Patients living where SCTN was available had a 25% higher likelihood of receiving tPA (adjusted relative risk [ARR] = 1.25, 95% confidence interval [CI] = 1.15-1.36) and lower risks of mortality (ARR = 0.91; 95% CI = 0.84-0.99) or discharge to skilled nursing (ARR = 0.93; 95% CI = 0.89-0.97). TS diffusion affects the structure of the health system serving a county, as well as the processes of care delivered in the emergency department; these changes are associated with measurable population health improvements. Results support a population benefit of TS implementation.