The 55-year-old woman was in her ground floor flat in 53 Main Road, Fairlie, when the coal lorry veered off the A78 into her home.
She is understood to have been trapped for more than three hours as specially trained rescue teams battled to save her. But she died at the scene.
Her 60-year-old husband suffered minor injuries in the crash and was taken to Inverclyde General Hospital, Greenock.
The couple are believed to be originally from Glasgow.
The 54-year-old driver of the lorry was also taken to hospital. He also suffered only minor injuries.
Police said one other man, who was in the building at the time, escaped unhurt.
The inside of the property became exposed after the impact of the crash reduced the wall to rubble.
Emergency teams were communicating with the woman while the rescue attempt was taking place.
Residents of the village, which has a population of around 1600, spoke of their shock at the crash.
Shaken Callum Calvey, 26, lives above the couple in the second floor flat. He said: "I was really worried about them, especially when I heard the woman was trapped.
"I think she was trapped under the lorry the whole time. They are a nice couple. I'm taken aback by everything."
Callum, a tree surgeon, was working in Kilbirnie when the lorry struck the property.
He said: "I just found out about it when my friend texted me a picture of my bath hanging outside the building. I have no idea what I'm going to do."
Fairlie resident Anna Conway, 41, said: "It was horrific.
"The whole community will be absolutely shocked."
Emergency services cordoned off the area.
The A78 was closed in both directions between the north of Fairlie and Hunterston and diversions were put in place.
Steve Graham, 56, chairman of Fairlie Community Council, said it was a "killer road".
He said: "We as a community council have been campaigning for years to stop the amount of traffic and heavy vehicles coming through the village to get to the Hunterston Coal Terminal.
"The road can't take it and it was just a matter of time before something like this happened on this killer road."
A spokeswoman from Strathclyde Police said the ground floor of the building was "seriously damaged" and deemed structurally unsound.
A North Ayrshire Council spokesman said: "We have sent a structural engineer to assess the condition of the building."