The red wind warning covers counties including Monmouthshire, Cardiff and Carmarthenshire in the south, Ceredigion, and Gwynedd and Anglesey in the north west.
People are being told to stay alert for flying debris and falling trees, along with large waves hitting sea fronts, homes and roads.
Power cuts and travel disruption are also possible, the Met Office added, with the M48 Severn Bridge already closed in both directions.
The RNLI has advised those living near or visiting the Welsh coast to exercise “extreme caution”.
The red warning will last from 03:00 GMT until 11:00 on Saturday, while an amber wind warning is in place from 01:00 until 21:00 on Saturday.
A number of weekend events have already been cancelled ahead of Storm Darragh’s arrival.
