Police are hunting at least two men who held up a van in a supposedly secure area near Terminal Four, escaping in another vehicle which bore the livery of British Airways.
It is understood the money was flown into Heathrow on a jet from Bahrain and bound for New York's JFK Airport.
The theft of $6.5m (£4.57m) happened in a secure area, beyond customs, at about 0630 GMT and it is possible the robbers had legitimate security passes.
The 35-year-old driver of the security van was forced from his van by the robbers who threw him to the ground and bound his wrists.
They then transferred eight red cargo cash boxes containing the currency into another similar British Airways van before driving undetected from the airport.
The raid only took a few minutes and the robbers left the supposedly secure Heathrow area undetected.
The van was later found abandoned and burnt out in Feltham, Middlesex, two miles away.
Local resident Marjorie Bacon, 61, saw the van explode.
"I looked out and heard an explosion. I thought one of the neighbours' cars had blown up."
Police said there was no trace of the money or the robbers. No firearms were seen in use during the robbery, a spokesman said.
Gold bullion
Detective Chief Superintendent John Coles, head of the Serious and Organised Crime Group said: " This is obviously an extremely serious incident which is why Specialist Operations Flying Squad are dealing with it. We are liaising with all relevant authorities."
The security van driver told officers at least two men attacked him. Police did not say how the robbers got in to the secure area or in which direction they fled.
The BA getaway van was genuine and had not been reported stolen.
BAA, which runs Heathrow Airport, was also investigating how the offenders gained access to a security-controlled zone.
A BAA spokeswoman said: "We do not know yet if the offenders had legitimate security passes or not."
The largest raid at the airport was the £26m Brinks Mat heist which remains Britain's biggest ever robbery.
The gang who seized the haul of gold bullion from the high security warehouse in 1983 were brought to justice but much of the gold has never been recovered.