Witnesses said it happened just after 18:30 GMT near Usk bridge in Brecon, Powys.
Dyfed-Powys Police confirmed it is searching for a 51-year-old woman.
Mid and west Wales fire crews from Brecon, Talgarth and Crickhowell are at the scene, as well as a boat from Swansea.
Mountain rescuers and a rescue helicopter are also involved.
The incident is ongoing.
It comes as 22 flood warnings are in place for Wales following a day of persistent and heavy rain.
Natural Resources Wales said rivers across the country had been affected, with up to 80mm (3in) expected to fall over the next 48 hours.
Areas worst hit by flooding include Gwynedd, Denbighshire, Conwy and Powys, and about 200 homes are without power.
River levels in some areas have reached almost record highs.
The River Vyrnwy at Meifod has risen to 12.3ft (3.75m), just 1.6in (4cm) below the 12.4ft (3.79m) recorded in February 2011.
Firefighters across the country have made a number of rescues, including:
Crews are also delivering sandbags to Penrhiwfer Road, Tonypandy, Rhondda Cynon Taff, after homes flooded.
Many rivers have burst their banks, and the worst affected include the Severn at Dolwen; rivers Vyrnwy, Mawddach and Wnion. The A458 from Llanfair Caereinion to Llanerfyl, in Powys, was closed because the River Banwy has burst its banks.
Mid and West Fire and Rescue Service has said it has been called out to 50 different incidents, all weather-related.
Pentyrch Primary School, Cardiff, has been closed due to "extensive water damage".
Arriva Trains Wales has cancelled some services.
A major search and rescue operation is under way following reports of a woman in the River Usk.