The capsule is meant to carry humans to an asteroid or Mars in the coming years.
No astronauts were on board the spacecraft, poised atop a Delta IV Heavy rocket at Cape Canaveral, now set to blast off at 8:26 am (1326 GMT), an hour and 21 minutes after the initial target time.
The launch window ends at 9:44 am (1444 GMT).
Tourists and space enthusiasts lined the area known as Florida's Space Coast to see the take-off at sunrise, and 27,000 guests were at the Kennedy Space Center for a close-up look.
The launch is the first of a US spacecraft meant to carry people into deep space in more than four decades, since the Apollo missions that brought men to the Moon.
With no American vehicle to send humans to space since the space shuttle was retired in 2011, some at NASA said the Orion launch has re-energized the US space program, long constrained by government belt-tightening and forced to rely on costly rides aboard Russian Soyuz spacecraft to reach the International Space Station in low-Earth orbit.
"We haven't had this feeling in a while, since the end of the shuttle program, (of) launching an American spacecraft from America's soil and beginning something new," said Mike Sarafin, lead flight director at NASA's Johnson Space Center in Houston.
The launch was due to propel 1.63 million pounds (739,000 kilograms) of spacecraft, rocket and fuel straight to space, where the capsule was due to make two laps around the Earth before splashing down in the Pacific Ocean around 11:30 am (1630 GMT).
The chief contractor of the Orion capsule is Lockheed Martin. The spacecraft was first designed to take humans to the Moon as part of NASA's Constellation program, which was cancelled by President Barack Obama in 2010, in favor or seeking new destinations in deep space.
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