Thame benefits from excellent road communications being strategically located adjacent to the M40 motorway. The A329 and A418 provide direct access to the A40 and to Junctions 7 and 8 of the M40 respectively, approximately 4 miles to the west.

The A418 is the principal arterial route to the north of the town and leads directly to Aylesbury, the A41 and the intersection with the A4146 and A505 to the north east. The A41 provides predominantly dual carriageway access to the M25 (Junction 20), the M1 (Junction 5) and London to the south east.