The launch marked NASA's first manned mission since the Columbia accident two-and-a-half years ago when a chunk of foam damaged the orbiter and caused it to burn up during re-entry, killing all seven astronauts on board.
"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, Godspeed -- and have a little fun up there," launch director Mike Leinbach told the astronauts just before liftoff, reported the Associated Press.
NASA employees, dignitaries and relatives of the seven astronauts aboard Discovery, as well as family members of the Columbia crew, watched as the shuttle rose from its launch pad at Cape Canaveral, Fla. and climbed into the hazy summer sky.
The shuttle launch, NASA's 114th, was the closest documented of any previous flight. Two chase planes and more than 100 cameras photographed the orbiter from all angles to detect whether any flying debris could put it in danger.
NASA will analyze the images and give a final verdict on whether Discovery is safe to return to Earth halfway through the mission, according to the AP.
The fuel gauge problem that postponed the planned July 13 launch of Discovery did not resurface before Tuesday's liftoff, the space agency reported, and the countdown proceeded smoothly.
The shuttle's mission, under veteran commander Eileen Collins, is to deliver supplies to the space station and test new safety and repair procedures, such as fixing damaged heat-resistant tiles while in orbit.
The other members of Discovery's crew are pilot James Kelly, and astronauts Soichi Noguchi from Japan, Stephen Robinson, Andrew Thomas, Wendy Lawrence and Charles Camarda.
Discovery is the first shuttle to fly after the Challenger exploded during liftoff in 1986.