The Thame played a key role in the English Civil War when John Hampden (the town's Member of Parliament) led the force of Parliamentarians successfully defending Aylesbury at the Battle of Holman's Bridge, where a small road crosses the river, in 1642.

The river passes by the 21st century small suburb of Watermead and around the north and west of Aylesbury, passing through farmland to the villages of Nether Winchendon and Chearsley before reaching the market town of Thame with which it shares its name.

Thame is about 15 miles (24 km) east of Oxford and grew from an Anglo-Saxon settlement beside the river.

At Holton mill the Thame turns southward and after passing the villages of Great Milton and Stadhampton, its valley widens.

[2] The small town's central streets are typically Anglo-Saxon, being not quite straight and set at various angles.