Atlantis blazed a path into history on Friday as it rocketed off the launch pad for a final time, marking the last-ever liftoff of the 30-year-old American space shuttle program.
The storied spacecraft is carrying a crew of four US astronauts toward the International Space Station on a 12-day mission to re-stock the orbiting lab.
The mission marks the end of an era in human spaceflight, leaving the United States with no spacecraft capable of taking astronauts to orbit and leaving Russia's three-seat Soyuz capsule as the sole taxi to the ISS.
"For a final time, good luck and Godspeed," said shuttle launch manager Mike Leinbach as Nasa gave the Atlantis the go-ahead to launch heading for the ISS, where it is due to dock early Sunday.
At least 750,000 people descended on Florida to catch a glimpse of history, braving snarled traffic and warnings of stormy weather that had briefly threatened to postpone the mission.
"All of us are addicted to going to space," said astronaut Cady Coleman, who recently returned from a six-month stint aboard the space station.
"We always want more. We would go all the time if we could," she told AFP.
Once opportunities for space travel are limited to catching rides aboard the Russian Soyuz at a cost of $51 million per ticket, astronauts will just need to draw on the patience they have always needed to have, she said.
Nostalgia, bitterness and sorrow mingled with pride at Kennedy Space Center as thousands of workers watched their cherished spacecraft sail into the skies for a final time.
As many as 8,000 people are losing their jobs with the closure of the shuttle program, which was ordered by former president Richard Nixon in the 1970s and launched its first mission in 1981.
Ahead of the launch, Nasa fended off criticism over the lack of an immediate successor to the shuttle and showed off the design of the Orion space capsule, the basis for a multipurpose crew vehicle that may someday travel to deep space.
Private companies like SpaceX, Boeing and Sierra Nevada are competing to become the first to build a next-generation space capsule that can take astronauts and cargo to the orbiting research lab.
But those plans are not likely to come to fruition before 2015 at the earliest.
President Barack Obama this week praised the shuttle for its long legacy in space exploration but said it was time to focus on new projects.
"Let's start stretching the boundaries so we're not doing the same things over and over again. But rather, let's start thinking about what's the next horizon, what's the next frontier out there," he said.
"In order to do that, we'll need some technological breakthroughs that we don't have yet."
Of the six US space shuttles, the prototype Enterprise never flew in space, Challenger exploded after liftoff in 1986 and Columbia disintegrated on its return to Earth in 2003. Fourteen crew members died in the two disasters.
Nasa plans to send the remaining three shuttles in the fleet -- Discovery, Endeavour and Atlantis -- to museums across the country to go on permanent display.