The Enterprise - the first US shuttle ever built - swept across the Manhattan skyline for a historic final flyover.
It left the Washington DC atop a Boeing 747 jet and was filmed flying past landmarks such as the Statue of Liberty.
The shuttle, which never actually went into space but was a prototype used for tests, has been on display at the Smithsonian Institute museum near Washington.
Nasa plans to put the shuttle on a barge in a few weeks and float it up the Hudson River to its final home, the Intrepid Sea, Air and Space Museum in New York City
Last week, space shuttle Discovery's dramatic flyover of Washington DC drew huge crowds of spectators.
It became the first of the retired shuttle fleet to enter a museum, the National Air and Space Museum's Steven F. Udvar-Hazy Centre in Virginia.
Later this year, Endeavour will move from the Kennedy Space Centre in Florida to the California Science Centre in Los Angeles.
The dramatic sky shows are part of Nasa's plans to send its fleet into retirement as it wraps up its shuttle program, which formally ended in July 2011.
The move, after 30 years of human space flight, leaves Russia and China as the only nations capable of sending astronauts to space.
Two other shuttles, Challenger and Columbia, were destroyed in accidents in 1986 and 2003. Both disasters killed everyone on board.
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