The River Misbourne rises in a field on the outskirts of Great Missenden in Buckinghamshire, passing through Little Missenden, Old Amersham, Chalfont St Giles, Chalfont St Peter and under the Chiltern railway line and the M25 motorway to its confluence with the River Colne just north of where the Colne is crossed by Western Avenue, the A40 road.

[3] Recent researchers have tentatively preferred Ekwall's guess, in which case the name Misbourne would once have meant something like 'river where water-plants/marsh-plants grow'.

[4][5]: 54–55, 73 In 1906 the Great Western Railway (GWR) constructed the Chalfont Viaduct to carry trains between London and High Wycombe across the river.

This state is only quasi-stable since in periods of low rainfall the water table drops below the level of the impermeable layer.

The upper part of the river was dry for over 3 years starting in November 2003 but re-appeared in February 2007 following several months of above-average rainfall which raised the water table.