Bolted to the top of a jumbo jet, NASA's youngest shuttle departed Kennedy Space Center at sunrise on the first leg of its flight to California.
Hundreds of people - astronauts, space center workers, tourists and journalists - gathered at the runway to bid Endeavour farewell following two days of rain delays. Crowds also lined the nearby beaches as the shuttle swooped in and out of low clouds in one final show.
Onlookers waved, saluted, blew kisses and cheered as Endeavour made one last swoop over its old landing strip, and then aimed for the Gulf of Mexico.
"You know what? I am feeling a tremendous amount of pride," said astronaut Kay Hire, who flew aboard Endeavour two years ago.
Several hours later, onlookers cheered excitedly as Endeavour flew over its landing place in Houston, not far from the home of NASA's Mission Control and all the astronauts. The jet carrying Endeavour landed a short time later at Ellington Field.
Endeavour will spend the night in Houston before continuing its journey to Los Angeles International Airport, where it's scheduled to land Friday.
In mid-October, Endeavour will be transported down city streets to the California Science Center.
If Endeavour couldn't remain anchored at the International Space Station, its main destination in recent years, then the science center is an ideal final stop, said astronaut Gregory Chamitoff. He will be on hand for Endeavour's arrival in Los Angeles.
Chamitoff grew up in California and flew to the space station in spring 2011 on Endeavour's final trip to orbit.
"I guess I didn't really know how I would feel until I woke up, and I think this is more exciting than it is sad for me," he said.
This is the last flight for a space shuttle. Atlantis will remain at Kennedy for display. Discovery is already at the Smithsonian Institution, parked at a hangar in Virginia since April.
Endeavour - the replacement for the destroyed Challenger shuttle - made its debut in 1992 and flew 25 times in space before retiring. It logged 123 million miles in space and circled Earth nearly 4,700 times.
The back-to-back delays in the ferry flight resulted in one day being cut from the Houston visit. The city was one of the bidders for a permanent shuttle exhibit, but had to settle for a mock-up from Kennedy. It lost out to New York City for the Enterprise, the shuttle prototype that was housed for years at the Smithsonian.
NASA retired its shuttle fleet last summer, under the direction of the White House, to spend more time and money on reaching destinations beyond low-Earth orbit. Asteroids and the planet Mars are on the space agency's radar for crewed missions.
Scott Rush, 54, of Crystal Beach, Texas, said he has been a fan of NASA since its earliest days and didn't want to miss a chance to see Endeavour, even though he's not happy it isn't staying in Texas.
Houston wasn't chosen as a shuttle retirement home. Instead, it got a full-sized replica.
"I think it's a pretty rotten deal, basically," Rush said. "The one we're getting is a toy. An important toy, but a toy nonetheless."