The village is entirely on foot. Santo Stefano di Sessanio has under 120 inhabitants and its medieval lanes are far too narrow for cars; you park at the edge of the village and walk everywhere from there. The whole place can be covered in a leisurely hour, though you will likely want to wander it several times at different hours of the day.
Hiking into the national park begins just outside the village. For the Campo Imperatore plateau -- the starting point for the higher Gran Sasso routes -- you need to drive about 10 kilometres up the mountain road. Day trips to Rocca Calascio, Castel del Monte, and L'Aquila all require a car.