South Wales Police said a car and a heavy goods vehicle collided on Llanharry Road, Llanharry, at about 08:30 BST on Saturday.
The Welsh Ambulance Service confirmed one person was pronounced dead at the scene and two others had been taken to Cardiff's University Hospital of Wales.
Their condition is unknown and the road was closed for several hours.
One person has died and two others have been taken to hospital following a "serious" crash in Rhondda Cynon Taff.