The jumbo jet headed to Las Vegas before departing again to a desert airfield near Phoenix. The aircraft, G-VROY, is known as Pretty Woman.
Like British Airways, Virgin is replacing its 747s with more fuel-efficient twin jets and has retired all its 747s early due to the pandemic.
It is not the end for G-VROY, as it has been purchased by US charter carrier Atlas Air.
Corneel Koster, the airline’s chief customer and operating officer, said: “The much-loved Boeing 747 has played an important role in Virgin Atlantic’s story.