Space shuttle Atlantis has rocketed away from its seaside launch pad in Florida on the 135th and final flight in the 30-year-old US shuttle programme.
Atlantis lifted off on its 12-day mission at 1529GMT after a quick fix to a last-minute technical problem.
The spacecraft is carrying four veteran US astronauts and a heavy load of supplies to restock the orbiting International Space Station.
Its return to Earth in about 12 days' time will mark the end of an era in human spaceflight, after which the United States will rely on Russia to send astronauts to space until a replacement US capsule can be built.
'The beginning of the end of the space shuttle era is this morning,' said NASA spokesman Allard Beutel.
At least 750,000 people have descended on Florida, with tourists eager to grab a glimpse of the final launch, but nostalgia has mingled with bitterness among the thousands of NASA employees set to lose their jobs.
'It is a sad time,' said NASA astronaut Terry Virts, reflecting on what he called the passion of many of his co-workers. 'The sad part about it is that we won't have an American ability to launch astronauts anymore.'
An abridged crew of four, Chris Ferguson, pilot Doug Hurley, flight engineer Rex Walheim and Sandy Magnus, began strapping into reclined seats on Atlantis' top deck shortly after 8am (1pm GMT+1).
Typically, two or three other astronauts would be seated in the windowless middeck during launch.
But NASA limited the crew to accommodate small Russian Soyuz capsules serving as escape vessels, should Atlantis too damaged during launch or while in orbit to safely return to Earth.
Previously, the US space agency had a second shuttle prepared for any potential rescue but Atlantis, which will be making the 135th and final flight of the programme, it has no shuttle backup.
Atlantis, which was set to be retired last year, is laden with food and other supplies critical to the International Space Station, a recently completed orbital research outpost 220 miles above Earth.
NASA added the final flight to buy time in case the commercial delivery firms hired to resupply the station starting next year run into problems with their new rockets.
Space Exploration Technologies, or SpaceX, which is owned by Internet entrepreneur Elon Musk, successfully tested its Dragon capsule in orbit last December and hopes to make it to the space station in a second test flight later this year.
The other cargo hauler being developed by aerospace company Orbital Sciences Corp, is expected to debut next year.
With the space shuttles retiring, the station and its six-member crew will need regular supply runs from both companies, in addition to deliveries from Russian, European and Japanese spacecraft.
All have just a fraction of the shuttle's 25,000-tonne lift capacity.
NASA has been steadily building the $100bn station over the last 11 years.
Completing it was the primary reason the United States decided to fix the shuttles and resume flying after the loss of Columbia and her crew in 2003.
With the space station assembly complete, the US wants to use the $4bn or so it has spent each year to maintain and operate NASA's three space shuttles to develop new spacecraft that can travel beyond the station's near-Earth orbit, where shuttles cannot go.
NASA filled the space shuttle Atlantis's external fuel tank ahead of its launch.