Mother-of-two Ellen Ruffle was 34 when she vanished without a trace in November 1969, in Motherwell.
The former primary teacher lived at the address in Annan Glade, from 1967 to 1969, with her husband Norman and two children, son Graham and daughter Rosemary.
Police teams armed with X-ray ground scanners and radar machines began digging up and scouring the property for clues shortly before 10am today.
A forensic tent was erected and specialist teams could be seen searching the garden, including the raised patio, as stunned neighbours in the quiet cul-de-sac looked on.
Shortly after her disappearance, her husband Norman took the two young children to South Africa.
He is understood to have now returned to Scotland and is believed to be helping police with their inquiries.
One local women, who asked not to be named said : "We have lived here for about 10 years now and had no idea about the history of that house. The first we knew about it was at 7am today when the police closed the road."
The operation which involves about a dozen officers was expected to last three or four days.
The dramatic development came after a tip-off to police that the missing mother of two may be buried somewhere in the property.
Superintendent Andy McKay, from North Lanarkshire police office, who is leading today's search said: "Here in Annan Glade we have specialist teams of search officers carrying out investigations at the property. This will include searches of the garden, garage and house.
He added: "Strathclyde Police regularly review historic cases and this is a long term suspicious missing person inquiry.
"There is an ongoing review at the moment of this case which has led us here today.
"I wish to state that the current householder is not linked to this investigation and I would also like to make an appeal on behalf of Ellen's children for anyone with any information about her whereabouts to come forward.
"I also want to reassure the public and assure them that we have taken these steps purely because we are trying to trace a member of their community."
Police launched an investigation at the time but found no trace of Mrs Ruffle, who was last seen visiting her mother's home in another part of Motherwell.
A police spokeswoman said: "We can confirm we will be conducting a search at a premises in Motherwell in relation to a long-term missing persons inquiry."