Atlantis is back in space for the first time since 2002.
Skies were partly cloudy as the shuttle thundered off the launch pad at 11:15 a.m. Eastern time.
It was the fifth launch attempt since August 27. Previous tries were scuttled by weather concerns and technical issues. The latest delay, Friday, was blamed on a faulty fuel tank sensor.
Minutes before lift-off, mission managers told the crew that "it looks like your long wait is over."
The Atlantis commander, Brent Jett, told controllers "it was worth the wait and we're ready to get to work."
NASA had several cameras trained on the shuttle as it lifted off, checking for any signs of hard foam breaking off the external fuel tank, the problem that doomed Columbia in 2003. There was no immediate word of any problems.
The Atlantis crew's mission is to resume construction on the international space station.