The shuttle lifted off from Kennedy at approximately 2:20 p.m. EDT.
Atlantis' final mission, officially known as STS-132, will see its crew conduct series of operations at the International Space Station during 12 days in orbit.
They'll drop off a Russian mini-research module, new batteries for the station's truss and dish antenna, and other replacement parts.
"Twelve days, three [spacewalks], tons of robotics—we're putting on spares that make us feel good about the long-term sustainability of the ISS," said Space Shuttle program manager John Shannon, according to a NASA news release.
"This flight has a little bit of everything, and it's been great preparation for the team," said Shannon.
The veteran crew includes commander Ken Hamm, pilot Tony Antonelli, and mission specialists Michael Good, Garret Reisman, Piers Sellers, and Steve Bowen.
Only two more shuttle flights will remain after Friday's launch.
The decision to cancel the shuttle program was made under the administration of former president George W. Bush, in part due to the 2003 destruction of Columbia, which exploded upon reentry into the Earth's atmosphere. All seven crewmembers were killed.
The program had previously lost a crew of seven when Challenger blew up shortly after liftoff on January 28, 1986.
President Obama has stuck with the cancellation plan, and in addition decided to kill a Bush initiative that would have seen astronauts return to the moon by 2020 in a new system comprising the Ares rocket and Orion crew capsule.
Obama's current fiscal budget proposal scraps Ares and retasks Orion as an emergency lifeboat that would be permanently docked at the ISS.
NASA engineers recently successfully tested an escape system for Orion (pictured) that's designed to jettison the capsule away from the launch pad in the event of an emergency like the one that claimed Challenger.
Critics of the plan to end the shuttle program insist its cancellation would leave the U.S. dependent on foreign countries for transportation to the ISS until a replacement vehicle is ready. Some U.S. lawmakers have introduced bills that would give the program a reprieve.
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