The collision happened on Main Street, in Fairlie, near Largs, at about 1.45pm today.
Strathclyde Fire and Rescue said a lorry had left the road and collided with a two-storey building.
The woman, who lived in one of the ground-floor flats of the two-up, two-down property, died at the scene.
A 60-year-old man who also lived in the flat and the driver of the truck, who is 54, sustained minor injuries. Both were taken to Inverclyde Royal Hospital.
One other man who was in the building at the time was evacuated unhurt.
No other vehicle was involved.
A 55-year-old woman who lived in one of the ground-floor flats of the two-up, two-down property died at the scene.
A 60-year-old man who also lived in the flat and the driver of the truck, who is 54, sustained minor injuries. Both were taken to Inverclyde Royal Hospital.
One other man who was in the building at the time was evacuated unhurt.
The ground floor of the building was seriously damaged and has been deemed structurally unsound, police said.
Eyewitness Steve Graham, chairman of Fairlie Community Council, said: "I walked up and had a look. There was a lorry deeply embedded into the corner of an old Victorian sandstone building.
"It is a coal lorry which for whatever reason has lost control and has ploughed into the house across the road."
He added: "This was an accident waiting to happen. There have been a number of near misses but nothing on this scale. It is a very narrow road with premises adjacent to the road.
"We in the community council have been complaining about the weight of traffic coming through the A78 which it's not built for. It would not meet current standards for a trunk road."
Strathclyde Fire and Rescue said large numbers of fire, police and ambulance personnel attended the incident, with resources drafted from across the west of Scotland, including Strathclyde Fire & Rescue firefighters from its Urban Search and Rescue team (USAR).
Two Major Incident Support Units (MSU) from Clydebank and Kilmarnock, and the Scottish Ambulance Service's Special Operations Response Team (SORT), also attended.
The A78 was closed in both directions between the north of Fairlie and Hunterston, and local diversions were put in place.
Superintendent Neil Kerr, Ayrshire division of Strathclyde Police, said: "At about 1.50pm an articulated lorry was travelling south on the A78 in the village of Fairlie where for some reason it has left the road and collided with the gable end of a house.
"Two people were inside the house, a 60-year-old man and a 55-year-old woman. Unfortunately and tragically the woman has died of her injuries.
"The 60-year-old man has been taken to Inverclyde hospital and the driver of the lorry is also at hospital. As far as I'm aware they have minor injuries.
"What we are doing is working with our partners to stabilise the building so we can re-open the road. However, what I can say is at this stage the road will be closed for some time and diversion routes are up and running."
