The 37-year-old woman and 42-year-old man were pronounced dead at the scene.
A further two people are in a critical condition and a third has been described as "serious".
The crash, which involved a silver Mercedes car and a white Vauxhall van, happened on the eastbound carriageway between Polmont and Linlithgow at about 21:00 on Friday.
Anyone who witnessed the crash is asked to contact police.
A Police Scotland spokeswoman said: "This has been a serious road traffic collision.
"We are keen to hear from anyone who witnessed it or who has information that can assist us in our inquiries."

Former Celtic boss Neil Lennon was quoted saying: "Nothing will prepare Warburton for his first taste of the Old Firm as a manager."
Warburton responded: "My background is one that's involved many pressurised situations in and out of football.
"If I can't deal with it, I shouldn't be doing the job, simple as that."
Rangers lost to Glasgow rivals Celtic in last season's League Cup in what was a one-sided contest.
Both sides lead their respective leagues, with Warburton close to clinching promotion to the top flight in his first campaign at Ibrox.
Asked about Lennon's comments, he continued: "I'm sure certain managers will say they have been misquoted or things have been taken out of context.
"You can't turn round and say you are ready for it but I'm also somewhat bemused by people who say you won't be able to deal with it.
"The fact is we've dealt with it all season. It's another game of football. We understand the significance of it. It's a highly-important game for the fans and it's a semi-final. I get all of that.
"But if you can't deal with that, don't be in the business."
Lennon also suggested Celtic will have the upper hand due to superior strength but Warburton does not fear being outmuscled at Hampden.
"Football is a game of opinions and that's the beauty of the sport, it incites so much opinions," said the former Brentford boss.
"But the fact is that we are very confident in our side and how we have fared this season. Our physicality in our minds is not in question."
Victory away to Raith Rovers on Saturday, coupled with a defeat for Hibernian at St Mirren, would deliver the Championship crown for runaway leaders Rangers.
"Raith are on a very good run of form right now so we need to go there and deliver a performance, otherwise we'll get hurt," added Warburton.
"The focus is very much on what we do. What happens away from us we can't control but what we can control is our own performance.
"On Saturday and Tuesday [at home to Dumbarton], the lads have the opportunity to take the club back to the top tier of Scottish football, so they are well aware of the significance and the expectations of the fans, the desire to get Rangers back to where they need to be.
"They recognise the opportunity but they've got to enjoy it. We don't want to limp over the line. We want to finish in a convincing manner."

The facilities at The Green, in Thorne, will undergo renovation after funding was secured from the Town Centre Innovation Fund and Doncaster Council.
Thomas Crapper, whose name is synonymous with public conveniences, was born in Thorne, in 1836.
The work, due to start on Monday, is expected to take six weeks to complete.
The leader of Thorne & Moorends Town Council Martin Williams said: "So many toilets are closing down all over the place so we thought that it would be good to refurbish some so all of the shoppers have got some decent facilities.
"I can't get him [Thomas Crapper] to open them but we could make it a memorial to him and put up a blue plaque."
Public toilets in South Parade will be opened while the work is completed.
According to the Thomas Crapper & Co website, despite popular thought Mr Crapper did not invent the WC but was behind a number of important innovations in sanitation.
Mr Crapper died in 1910 and is buried in Elmers End Cemetery, in Beckenham, Kent.
A nine-year-old girl has died, along with a man and woman, in a crash on the M9 in West Lothian.
[NEXT_CONCEPT]
Rangers manager Mark Warburton insists he has the experience to deal with the pressure of facing Celtic in next month's Scottish Cup semi-final.
[NEXT_CONCEPT]
A Â£30,000 project to refurbish the public toilets in the birthplace of legendary lavatory maker Thomas Crapper is set to begin.