During a scheduled 6½-hour spacewalk, astronauts Michael Fossum and Ronald Garan Jr. prepped the $1 billion lab for installation by removing power and heating cables and restraints that connect it to the shuttle.
"Wow, this is incredible," Garan, a spacewalking rookie, said just after he stepped outside.
Astronauts working from inside will use the space station's robot arm later in the day to lift the lab from the shuttle and anchor it to the station.
Later in the spacewalk, the astronauts were going to try out some cleaning methods on a jammed solar rotating joint that has hampered energy production at the space station since last fall. The joint enables the space station's solar arrays, which provide electrical power, to rotate and track the sun.
"It's going to lead to a really busy day for all of those guys," said Emily Nelson, a space station flight director.
The start of the spacewalk was delayed nearly an hour as a faulty communications cap - which allows spacewalkers to talk with other crew members and controllers on the ground - was replaced in Fossum's spacesuit.
The lab is named Kibo, Japanese for hope. At 37 feet long, it is bigger than the U.S. and European labs already attached to the space station. The Japanese lab also has a pair of robot arms, the larger of which flew up on this shuttle mission.
"We're looking forward to a great day, an exciting day to install the Japanese Kibo module," said Japanese astronaut Akihiko Hoshide, who will help move the lab with the station's robotic arm.
A separate storage room loaded with Kibo equipment went up in March. A porch for outdoor science experiments and the smaller robot arm will fly next year.
During their first major task, Fossum and Garan removed protective covers and various power and heater cables on a 50-foot inspection boom that had been attached to the space station.
After the boom was released, astronauts used the station's robotic arm to hand it off to the shuttle's robotic arm.
The laser-equipped boom is usually attached to the shuttle's robotic arm and used to conduct a detailed inspection of the spacecraft's wings and nose. The inspection is one of the safety measures put in place by NASA after the 2003 Columbia accident to check for launch damage.
Discovery didn't have enough room for the inspection boom; Kibo filled the entire payload bay. So the last shuttle crew left one behind at the space station in March.
The shuttle astronauts, who arrived at the space station on Monday, will use the boom next week to check Discovery for any damage that could endanger them during re-entry.
Imagery experts are poring over the 302 digital pictures that the space station crew took of Discovery's belly right before the docking. About five pieces of foam insulation broke off Discovery's external fuel tank during liftoff, but are not believed to have caused any damage.
NASA, meanwhile, is investigating the worst launch pad damage in 27 years of space shuttle flight.
A large section of the flame trench - 20 feet by 75 feet - broke apart, and chunks of the large heat-resistant fire bricks and concrete mortar were scattered all the way past the chain-link fence 1,800 feet away. The fence was damaged in places.
None of the debris appeared to hit Discovery, said LeRoy Cain, chairman of the mission management team.
The flame trench - dating back to the 1960s Apollo era and designed to deflect the exhaust of the booster rockets - is inspected regularly and undergoes periodic repair, Cain said.
NASA does not need to use the pad again until the next shuttle launch in October. That mission - the final trip to the Hubble Space Telescope - should not be delayed as a result of the damage, Cain said.