Montepulciano has no railway station. The nearest train connections are at Chiusi (on the Rome–Florence main line, about 20 kilometres away) and Montepulciano Stazione in the valley below, served only by infrequent regional services. From Chiusi, buses connect to the town.
By car is the most practical approach: Montepulciano is about 120 kilometres south of Florence and 60 kilometres north of Orvieto, accessible from the A1 motorway via the Valdichiana exit. Siena is about 65 kilometres to the northwest. Parking is available outside the town walls; most of the historic centre is restricted to residents.