After a special goodbye ceremony, they floated out of the International Space Station for the last time.
They left behind two commemorative items for future space station occupants. One was an American flag flown on the first shuttle 30 years ago, the other a model of the shuttle.
Atlantis is set to undock from the space station on Tuesday and land back on Earth on Thursday.
It was a heartfelt goodbye for the two crews, numbering 10 astronauts in all from three countries.
"We brought the best monument we could possibly find, and that's a space shuttle model," Atlantis' commander, Christopher Ferguson said.
The model, signed by senior shuttle managers and flight directors, was hung near the hatch.
"What you don't see are the signatures of the tens of thousands who rose to orbit with us over the past 30 years, if only in spirit," Ferguson added.
Space station astronaut Michael Fossum accepted the model "as one of the greatest testaments to the shuttle's incredible capability."
The Associated Press contributed to this story.