Its destination is the International Space Station, which was soaring over the South Pacific at the time of liftoff. The shuttle should catch up with the orbiting complex and its six residents Sunday.
More than 40,000 guests -- the biggest launch-day crowd in years -- descended on the Kennedy Space Center and the roads leading into it, all of them eager to witness Atlantis' last launch. The shuttle obliged, roaring off the pad right on time.
"Good luck, godspeed and have a little fun up there," launch director Mike Leinbach told the astronauts just before liftoff. He said he was speaking on behalf of all those who have worked on Atlantis since the beginning.
"If you don't mind, we'll take her out of the barn and make a few more laps around the planet," replied commander Kenneth Ham.
The astronauts -- all repeat space fliers and all men -- couldn't resist a little humor before they got down to business. They showed up for their steak and cheeseburger breakfast wearing blue and black smoking jackets, white shirts and black bow ties. It was probably the most formal attire ever worn by astronauts on launch day, even it was just for a quick photo.
The only concern during Friday's countdown involved a small ball bearing found in Atlantis' payload bay earlier this week. Engineers scrambled to determine the bearing likely came from a spacewalk camera, and cleared the launch with just minutes remaining.
The 12-day mission is the last one for Atlantis, the fourth in NASA's line of space shuttles. Only two flights remain after this one, by Discovery and Endeavour. NASA plans to end the 30-year program by the end of this year.
Atlantis rocketed into orbit for the first time in 1985. This will be its 32nd trip and the 132nd shuttle flight overall. The shuttle is loaded with fresh batteries and a Russian-built compartment for the space station.
The 20-foot-long module -- named Rassvet in Russian, meaning Dawn -- is crammed with food, laptop computers and other U.S. supplies, part of the deal worked out between the two countries' space agencies.
Ham and his men will install the compartment on the space station, and carry out three spacewalks to replace six old batteries and hook up an antenna and other spare parts.
Launch spectators included late-night TV host David Letterman, who toured the space center Thursday.
Dozens of Russians also were on hand, as well as about 150 Twittering guests. This is the second time NASA has opened Kennedy's media complex to so-called tweeters on launch day.
President Barack Obama wants NASA to focus on getting astronauts to an asteroid by 2025 and into orbit around Mars by 2035. He canceled the previous administration's Constellation program, considered a continuation of the 1960s Apollo moon program.
It was NASA's fourth shuttle liftoff in six months.
Now the pace will slow a bit. Discovery isn't due to fly until September, followed by Endeavour in November -- at the earliest.
Payload issues may bump the last mission into 2011.
There's a chance that Atlantis could fly again after it returns to Earth on May 26. The shuttle will be prepped in case a rescue mission is needed for the last flight, by Endeavour. Assuming there's no emergency, Atlantis could be used for another supply run if the White House approves it, and that would close the shuttle program for good.
Atlantis ultimately will head to a museum somewhere in America. So will the other two shuttles.
Under the Obama plan, NASA astronauts assigned to long station missions will keep hitching rides aboard Russian Soyuz rockets until U.S. private enterprise can develop spacecraft to safely get humans into orbit.
NASA expects to keep the space station running through 2020.