The Towamba River rises near Coolangubra Mountain, below Mount Marshall on the eastern slopes of the South Coast Range, part of the Great Dividing Range, approximately 9 kilometres (5.6 mi) north of Coolangubra Mountain.

The river flows generally southeast and then northeast, joined by twelve tributaries including the Mataganah Creek and Wog Wog River, before reaching its mouth, emptying into Nullica Bay, within Twofold Bay, and spilling into the Tasman Sea of the South Pacific Ocean, east of Boydtown.

[2] The catchment area of the river is 1,026 square kilometres (396 sq mi) with a volume of 2,050 megalitres (72×10^6 cu ft) over a surface area of 2.0 square kilometres (0.77 sq mi), at an average depth of 1.1 metres (3 ft 7 in).

The river flows through extensive parts of the South East Forest National Park in its upper reaches.

In its lower reaches, the river forms the northern boundary of Mount Imlay National Park.