Cape Canaveral, Fla. ? With a cry from its commander to “light this fire one more time,” the last shuttle thundered into orbit Friday on a cargo run that will close out three decades of both triumph and tragedy for NASA and usher in a period of uncertainty for America’s space program.

After some last-minute suspense over the weather and a piece of launch-pad equipment, Atlantis and its four astronauts blasted off practically on schedule at 11:29 a.m., pierced a shroud of clouds and settled flawlessly into orbit in front of a crowd estimated at close to 1 million, the size of the throng that watched Apollo 11 shoot the moon in 1969.

It was the 135th shuttle flight since the inaugural mission in 1981.

“Let’s light this fire one more time, Mike, and witness this great nation at its best,” Atlantis commander Christopher Ferguson told launch director Mike Leinbach just before liftoff.

Atlantis’ crew will dock with the International Space Station on Sunday, deliver a year’s worth of critical supplies to the orbiting outpost, and bring the trash home. The shuttle is scheduled to land back on Earth on July 20 after 12 days in orbit, though the flight is likely to be extended to a 13th day.

After Atlantis’ return, it will be lights out for the shuttle program. Thousands of workers will be laid off within days. The spaceship will become a museum piece like the two other surviving shuttles, Discovery and Endeavour. And NASA will leave the business of building and flying rockets to private companies while it turns its attention to sending humans to an asteroid by about 2025 and Mars a decade after that.

It will be at least three years — possibly five or more — before astronauts are launched again from U.S. soil.

Leinbach said that as Atlantis disappeared in the clouds, he and a friend in the control center put their arms around each other and said: “We’ll never see that again.”

Inside the room, “it seemed like we didn’t want to leave,” Leinbach said. “It was like the end of a party, and you just don’t want to go, you just want to hang around a little bit longer and relish our friends and what we’ve accomplished. So it was very special, lots of pats on the back today.”

The space shuttle was conceived even as the moon landings were under way, deemed essential for building a permanent space station. NASA brashly promised 50 flights a year — in other words, routine trips into space — and affordable service.

Shuttle crews built the International Space Station, repaired several satellites in orbit and, in a feat that captured the public’s imagination, fixed the Hubble Space Telescope’s blurry vision, enabling it to see deeper into the cosmos than ever before.

But the program suffered two tragic accidents that killed 14 astronauts and destroyed two shuttles, Challenger in 1986 and Columbia in 2003. NASA never managed more than nine flights in a single year. And the total tab was $196 billion, or $1.45 billion a flight.

This day of reckoning has been coming since 2004, a year after the Columbia tragedy, when President George W. Bush announced the retirement of the shuttle and put NASA on a course back to the moon. President Barack Obama canceled the moon project in favor of trips to an asteroid and Mars.

But NASA has yet to work out the details of how it intends to get there, and has not even settled on a spacecraft design. The lull that the end of the shuttle program will bring is unsettling to many space-watchers.

The space shuttle demonstrates America’s leadership in space, and “for us to abandon that in favor of nothing is a mistake of strategic proportions,” lamented former NASA Administrator Michael Griffin, who led the agency from 2005 to 2008.