En route to John F. Kennedy International Airport, the retired shuttle flew at low altitude along the river, giving residents of New York and New Jersey an extraordinary view of the craft, which will be put on display at a New York museum.
After three decades, the United States retired its space shuttles last year after building the $100 billion International Space Station, a 15-nation project. It will begin work on a new generation of spaceships to carry astronauts beyond the station's 384km-high orbit.
The Enterprise flight took off from Washington Dulles International Airport outside the nation's capital. The flight was rescheduled from Wednesday due to unfavourable weather.
It flew past the Statue of Liberty, up the Hudson River and over the George Washington Bridge before turning to land to the cheers of school children clad in astronaut garb. Also on hand for its arrival were members of its original flight crew.
"I am proud that the Enterprise is going to have a great home here," said retired Air Force Major General Joe Engle, who commanded the first flight crew that conducted test flights with the Enterprise in the late 1970s.
"You've got a tremendous piece of machinery here," he said.
Actor Leonard Nimoy, who played Spock on the "Star Trek" television series and movies, was on hand for the arrival. He recalled watching as Enterprise, which bears the same name as the starship from "Star Trek," was unveiled in California.
"I was there in September 1976 when they rolled it out of the hangar," he said. "The Air Force band was playing the theme from Star Trek - da-da-da-da-daaaaa. I love it."
Nimoy said "Star Trek" fans waged a letter-writing campaign to persuade then-President Gerald Ford to name the shuttle Enterprise. "'Star Trek' fans can be very persuasive," he said.
Flashing a Vulcan gesture from "Star Trek," he said: "Live long and prosper."
A prototype orbiter that was used for atmospheric test flights in the 1970s but never on a space mission, Enterprise is scheduled later to be moved by barge up the Hudson for display at the Intrepid Sea, Air and Space Museum in Manhattan.
It will be lifted by crane onto the Intrepid, an aircraft carrier that has been a museum since 1982.
NASA has been flying the shuttles to cities around the nation for display.
On April 19, space shuttle Discovery was flown over Washington on its way to being displayed at the Smithsonian's National Air and Space Museum annex in Virginia, where it replaces Enterprise.
Sister ship Endeavour will head to the California Science Center in Los Angeles in the fall, while Atlantis will go on exhibit at the Kennedy Space Center Visitor Complex in Florida.
