San Quirico d'Orcia is most easily reached by car. It sits on the SR2 (Via Cassia), the old road that runs south from Siena toward Rome. From Siena the drive takes about an hour; from Rome it is about two and a half hours.
Public transport options are limited. Buses run from Siena via Buonconvento to San Quirico, but the service is infrequent and timetabled around local needs rather than tourist convenience. Check the Tiemme bus timetables before relying on this option.
The nearest train stations are at Buonconvento (on the Florence–Rome line) and Chiusi, both of which require a taxi or bus connection to reach San Quirico.