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The Mid Infra-Red Instrument (Miri) was flown out of London Heathrow on a British Airways jet, bound for Nasa's Goddard Space Flight Center.
JWST will be the successor to Hubble, and aims to track down the very first stars to shine in the Universe.
Miri, built by a pan-European consortium led from the UK, will play a central role in that endeavour.
The 120m-euro (£95m; $150m) instrument, tucked inside its protective box, was loaded on to BA flight 217 for Washington Dulles International Airport.
The ride across the Atlantic was due to last about 7.5 hours.
On landing, Miri will be driven the relatively short distance around the US capital's "Beltway" to Goddard where it will be unpacked on Wednesday.
Nasa engineers will then integrate Miri into the telescope structure prior to further testing.
"Miri's box is a standard environment-controlled air-freight container, but we built a special structure inside to hold this incredibly valuable instrument," explained Piyal Samara-Ratna, the mechanical engineer from Leicester University overseeing the transfer.
"It has vibration isolating mounts to prevent any shock loads going through Miri. We also have sensors in there as well, so we would know if it got bumped.
"It's impossible to insure something like Miri, which represents the time and effort of so many people in Europe and the United States."
JWST is a Nasa project, with key inputs from the European and Canadian space agencies.
As well as two of its four instruments, Europe is providing the Ariane 5 rocket to put the observatory in space.
It will carry a 6.5m primary mirror (more than double the width of Hubble's main mirror), and this must be folded to fit inside the Ariane launcher. So too must the giant sunshield that will protect Webb's sensitive vision.
The telescope is being tuned to see the cosmos in the infrared. This is the part of the electromagnetic spectrum in which the first luminous objects - the first stars and galaxies - should be detectable.
Miri was sent to Heathrow from the Rutherford Appleton Laboratory in Oxfordshire where its final assembly took place.
It was accompanied by 15 other boxes of support equipment.
The main container carried the flags of all the European nations that have worked on the instrument and the signatures of its principal scientist, Prof Gillian Wright, and its project manager, John Thatcher from the Astrium space company. A message read simply, "First and best".
It is expected the other Webb instruments will also finish their builds very shortly.