The entire length of the river (Welsh: Afon Wysg) downstream of Usk Reservoir has been designated a site of special scientific interest (SSSI) and special area of conservation (SAC) .  The designation is in recognition of its importance for various fish species - three species of lamprey, the twaite shad, the bullhead and the Atlantic salmon.  It is also important for its otter population.

With little development along its length, the quality of the Usk's water is high and there is relatively little disturbance from man.  The designation extends to most of its tributaries making the entire catchment a very valuable one for Welsh wildlife.

The river rises as a small stream at Waun Lwyd some 500m up on the northern flanks of the Black Mountain.  Flowing north it soon enters the Usk Reservoir, dammed in 1955 to supply water to Swansea.  The emergent river flows east through Cwmwysg, passing Trecastle, Sennybridge and Llanspyddid before reaching Brecon.  Its course turns to the southeast as it leaves Fforest Fawr Geopark bound for Abergavenny, Usk and eventually the sea at Newport.

For part of its course the river has a rocky bed of St. Maughan's Formation sandstones and mudstones.  Other sections of the Usk valley are filled with river sands and gravels and with glacial deposits. 

In fact the ice ages have caused the river to dramatically alter course at least once or twice.  At Brecon it is thought that earlier versions of the Usk flowed to the north of the present route from Aberyscir via Cradoc and both north and south of Pen-y-crug at different stages.