Atlantis is poised to blaze a path into history Friday when it propels toward the heavens on the last-ever mission of the 30-year-old American space shuttle program.

With the launch scheduled for 11:26 am (1526 GMT) despite a gloomy weather forecast, the storied spacecraft will tote a quartet of 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, after the process of filling the external fuel tank began at 2:01 am (0601 GMT).

At least 750,000 people descended on Florida as tourists were eager to grab a glimpse of the final launch, but nostalgia 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 coworkers. "The sad part about it is that we won't have an American ability to launch astronauts anymore."

Virts, who piloted the shuttle Endeavour's mission to the orbiting lab in February 2010, said the absence of a project to replace the shuttle has left many people reeling.

"People are not inherently upset about the shuttle ending -- it has been going for 30 years, it could probably fly for another 30 years -- but we understand that sometimes you need to move on to the next thing," he said.

"We had the next thing and it got canceled, and it is tough to end something without having a follow-on," Virts added, referring to the Constellation program aimed at returning astronauts to the moon.

The program was axed by President Barack Obama last year in favor of focusing on deep space missions that could see Americans explore an asteroid and potentially Mars in the coming years.

NASA has salvaged plans for the Orion space capsule, developed as part of Constellation, with the prospect of using it as the basis for a multipurpose crew vehicle that can venture into deep space.

Meanwhile, 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.

Those plans are not likely to come to fruition before 2015 at the earliest.

"All of us are addicted to going to space," said astronaut Cady Coleman, who recently returned from a six-month stint aboard the International 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.

"If it (space travel) is the only thing you want to do... this is not the right job," she said. "The job of an astronaut is much, much broader than going into space."

Earlier this week, Obama 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."

Meanwhile, space fans braved the rain and engineers forged ahead with plans for the 135th and final shuttle mission despite weather forecasts that predicted just a 30 percent chance of good conditions for liftoff.

"My whole life I grew up with the space shuttle," said Nicole Solomon, 35, a producer who is visiting from California to watch Atlantis blast off, and who plans to follow every detail of the shuttle's last adventure in space.

"I'll watch the mission and I'll watch the landing and probably shed a few tears."

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