The mother, father and two pre-school children, who are understood to be from West Lothian, were pronounced dead at the scene after their Fiat collided with an aggregates lorry on the A801 near Polmont yesterday afternoon.
The two adults were in their twenties and the youngsters were under three.
The lorry driver was shaken but uninjured, police said.
The tragedy happened near the Lathallan roundabout by junction four of the M9 at 2.20pm.
Three Scottish Fire and Rescue Service crews from Bo'Ness, Falkirk and Larbert were sent to the incident and firefighters cut free one casualty from wreckage.
Superintendent Iain Murray, head of road policing, confirmed that two girls under the age of three and their parents - both in their twenties - had been killed in the crash.
He said immediate family had been informed but police were still trying to get in touch with friends and relatives.
He added: "These are tragic circumstances for all concerned - family and friends have lost loved ones. To see a whole family unit taken out is awful. This is terrible. The circumstances are horrendous."
Superintendent Murray said they were particularly keen to trace a silver people carrier that was seen near the site of the crash.
The road, which runs from the Bowhouse roundabout near Maddiston to the roundabout that accesses Polmont and the M9, was closed for several hours as Police Scotland forensic investigators surveyed the screened-off scene.
A series of diversions were put in place and Traffic Scotland and the AA reported severe disruption around the Polmont area at the junction with the A801 and the M9 into yesterday evening.
The A801 links the M8 and M9 and has been the scene of numerous accidents.
In 2012 MP for Linlithgow and East Falkirk Michael Connarty spoke in Parliament about the need for money to be spent making the road safer.
He told Parliament the A801 was "probably the most dangerous road in Scotland when it is not snowing".
He was reported as saying he had been calling for the "desperately needed" upgrade for more than 20 years.
He said: "Upgrading this road was one of my first campaigns as an MP in 1992. It stuck out like a sore thumb as a missing link in the road network."
He added: "There have been many bad accidents on this road. If you don't know the area, the dip can be very deceptive."
However, a local farmer, who owns the adjoining field but did not want to be named, said it was not a particularly dangerous stretch of road.
He said: "It's tragic, especially since a young family was involved. It will be very upsetting for their relatives and the locals. People fly up and down the road, but I would not say it's dangerous.
"I just saw the road closed when I came along the field and I saw the flashing lights."