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

With the launch scheduled for 11:26 am (local time) 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 (local time).

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 cancelled, and it is tough to end something without having a follow-on," Virts added, referring to the Constellation programme aimed at returning astronauts to the moon.

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