"Thank you guys for the module and all your help," space station commander Peggy Whitson said as Discovery pulled away from the orbiting outpost.
"Drive safe, now," said Dan Tani aboard the space station.
"Thanks!" replied shuttle commander Pam Melroy.
Now the Discovery crew takes one last look at its heat shields to make sure it's in good shape for the ride home, reports . They'll scan the wings and nose cap, looking for any dents and dings that may have come from micrometeoroid hits during nearly two weeks in orbit.
Discovery is due back in Florida Wednesday. The crew arrived at the station on Oct. 25 and quickly accomplished the ambitious tasks of installing a new pressurized compartment and moving a massive solar power tower.
But their toughest assignment emerged when one of the newly installed tower's wings ripped in two places as it was being unfurled.
Fearing the damage could worsen and the wing could be ruined, NASA sent a spacewalking astronaut far from the safety of the station to make emergency repairs on what amounted to a live electrical generator.
Saturday's history-making spacewalk has allowed the space agency to push forward with plans to launch the shuttle Atlantis and its major cargo - a new European lab - in December.
Shortly after undocking, the shuttle will fly a full lap around the station, primarily so crew members can take pictures of the outpost's new configuration. Engineers are particularly interested in seeing how the newly mended solar wing is affected by the vibrations of undocking.
The 10 astronauts aboard the station and shuttle bid each other tearful farewells Sunday before closing the hatches to prepare for Discovery's departure.
It was an especially poignant goodbye for astronaut Clayton Anderson, who is headed home after five months in orbit. He was replaced on the station by Daniel Tani, who is starting a two-month mission.
The two commanders, Whitson and Melroy, also were teary-eyed as they hugged one another. They are the first women to simultaneously manage two spacecraft in the 50-year history of spaceflight.
The shuttle dropped off nearly 34,000 pounds of gear at the space station, most notably the school bus-sized compartment that will serve as a docking port for future laboratories.
Whitson and her crew plan to move the compartment, named Harmony, to its permanent location next week.
Now the station is set to receive the European Columbus lab next month, and the Japanese Kibo lab early next year, reports King.