Karpenisi is in central Greece with no train service and no airport — it is a car destination. The most direct route from Athens takes around three hours via the E65 motorway north to Lamia and then west on mountain roads through Makrakomi. The road is well-surfaced but demanding in the final stretch, with long winding climbs through the Tymfristos foothills.
KTEL buses run from Athens (Liosion terminal) and from Lamia several times daily, taking around three and a half hours from Athens. The bus drops passengers at the main square in Karpenisi town. From Thessaloniki, the most practical route is via Lamia or Agrinio depending on direction.
There is no convenient public transport into the Agrafa villages or to most of the surrounding gorge trailheads — a rental car or a local tour operator is necessary for anything beyond the town itself.