At stake were not only the lives of the astronauts, but also America's pride in its technological prowess and the fate of the US space program.
"Our long wait may be over. So on behalf of the many millions of people who believe so deeply in what we do, good luck," launch director Mike Leinbach told the astronauts before liftoff.
Space program employees and relatives of the Discovery and Columbia crews watched nervously as the shuttle rose from its pad at 10:39am (1439 GMT), climbed into a hazy midsummer sky, skirted two decks of clouds and headed out over the ocean in the most scrutinized launch in Nasa history.
Two chase planes and more than 100 cameras documented the ascent from every possible angle to capture any sign of flying debris of the sort that doomed the last flight.
Safety verdict later
There was no immediate word from Nasa on launch damage to the spacecraft. The multitude of images will not be fully analyzed - and Nasa will not give a final verdict on whether Discovery is safe to return to Earth - until halfway through the 12-day flight.
The fuel-gauge problem that thwarted a launch attempt two weeks ago did not resurface before liftoff, and the countdown was smooth. The space agency had been prepared to bend its safety rules to get the shuttle flying.
Nasa did not immediately say how the sensors performed during the climb to orbit, but everything appeared to go well.
"Godspeed - and have a little fun up there"
Nasa launch director
A TV camera mounted on Discovery's giant orange external fuel tank provided a view of the shuttle's climb to orbit and the tank being jettisoned back toward Earth as designed.
During the mission, commander Eileen Collins and her crew will deliver supplies to the international space station and test new techniques for inspecting and patching the shuttle in orbit.
The 114th shuttle liftoff came after painful self-examination on Nasa's part, extensive safety modifications to the spacecraft and months of hurdles and setbacks.
A launch attempt on 13 July was scrapped after one of four critical hydrogen-fuel gauges in the external tank failed two hours before liftoff.
Hundreds of engineers chased the problem, which had cropped up three months earlier in a fueling test. In the end, they could not fully explain the trouble but fixed some electrical grounding inside the shuttle in hopes that might solve it.
The space agency said it was prepared to relax a rule, instituted after the 1986 Challenger explosion, that required that all four gauges be working for launch.
Nasa Administrator Michael Griffin said the shuttle was as safe as Nasa could make it but was still a risky venture.
"Some things simply are inherent to the design of the bird and cannot be made better without going and getting a new generation of spacecraft. That's as true for the space shuttle as it is for your toaster oven," he told journalists on the eve of launch.
Columbia was brought down by a suitcase-size piece of foam insulation that broke off the big external fuel tank during liftoff and caused a gash that allowed hot gases into the wing during the return to Earth 16 days later on 1 February 2003.
But Nasa could barely make out the blow in the photographs of the launch because the few available images were poor.
The space agency added more and better surveillance cameras for Discovery's launch and sent up a pair of camera-equipped planes to chase the flight.
Pictures will also be taken from space, by the astronauts and spy satellites.
Also, once Discovery arrives at the space station on Thursday, the two residents will photograph the shuttle as it completes a slow flip.
The Discovery crew aborted a launch
two weeks ago on safety grounds
Nasa's chief acknowledged a lot is riding on the flight: the shuttle program, the space station program, President George Bush's plan to send astronauts back to the moon and on to Mars - and seven lives.
"It's about hope, it's about imagination, it's about the
future, and when you take away a great space program, you take away a lot of people's future," Griffin told reporters.
"What's riding on this flight is people's hope for the future."
Thousands descended on Cape Canaveral for the launch, including first lady Laura Bush, Florida Governor Jeb Bush, her brother-in-law, and members of Congress, as well as relatives of the 14 fallen Columbia and Challenger astronauts.
In addition to Collins, the crew members are pilot Jim Kelly, Soichi Noguchi of Japan, Stephen Robinson, Andrew Thomas, Wendy Thomas and Charles Camarda.
Discovery is hauling an almost three-year back order of supplies and replacement parts to the half-built space station and its two residents. Construction has been on hold since the last shuttle visit in late 2002.