The shuttle and its crew of seven, including a Japanese astronaut, are due back on Earth on Saturday.
"We wish them the best with their expedition and we hope we left them a better, more capable space station than when we arrived. Sayonara," shuttle commander Mark Kelly told the space station crew before leaving.
"We wish you guys a terrific flight back, an awesome landing and look forward to seeing you on the ground," responded Gregory Chamitoff, the station's newest crew member.
After the shuttle undocked from the space station, pilot Ken Ham backed Discovery away from the orbiting outpost and prepared to guide it through a loop around the orbiting complex so the crew can take pictures of its new look. Once that is done, the shuttle will fire its engines and begin its journey home.
Besides delivering the new lab, the shuttle also dropped off Chamitoff. He traded places with astronaut Garrett Reisman, who lived aboard the orbiting outpost for three months. Chamitoff will stay on the station for six months.
The hatches between the shuttle and station were closed Tuesday in preparation for the departure. Before the doors were shut, the seven Discovery members and the three-man station crew held a brief ceremony in which they shook hands and hugged goodbye.
"It's really sad to see you guys go for me. But I'm looking forward to the adventure ahead," said Chamitoff, 45, an aeronautics researcher.
Reisman, 40, a mechanical engineer, lightened the moment with a bit of humor.
"I managed not to break anything really expensive," he said. "I'm leaving now with the station in good hands and with a tremendous feeling of satisfaction."
Discovery's crew delivered and installed the new lab named Kibo, Japanese for hope, to the space station.
The 37-foot lab, about the size of a bus, is the biggest room at the space station. Kibo also has a storage closet and a 33-foot robotic arm.
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The $1 billion lab's third and final section
-- a "porch" for exterior experiments -- and a second, smaller robotic arm will be delivered next year.
Before returning home, Discovery's astronauts will pull out the laser-tipped inspection boom that they retrieved from the space station after it was left by another shuttle in March, and survey their ship's wings and nose cap.
The laser survey normally is conducted the day after liftoff, but Discovery didn't have room for the inspection boom because of the giant Kibo lab that filled its payload bay.
The inspection, which will look for any damage from debris generated during the May 31 launch or from micrometeorites in orbit, is one of the safety measures put in place by NASA after the 2003 Columbia accident. Columbia was destroyed during re-entry as a result of a gashed wing.
Flight director Matt Abbott said photography and data collected so far on the shuttle's thermal protective shield indicate the ship is in good shape.
"We haven't seen anything that gives us any indication of concern at this point," Abbott said.
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