The Dreamliner left the runway at Paine Field north of Seattle just after dawn, flying into gusty, slate-gray skies, bound for Tokyo Haneda Airport. The flight will take about nine hours and 40 minutes.
Three years behind schedule, the Dreamliner will go into service for Japan's All Nippon Airways on October 26.
The 787 Dreamliner is a light-weight aircraft with an airframe made of carbon composites. It promises greater fuel efficiency and passenger comforts than similarly sized aluminum planes.
Boeing has wrestled for years with delays caused largely by problems with a large number of companies that supplied parts for the plane.
Now the company faces another monumental task of producing the airplane at a rate of 10 a month by the end of 2013. Boeing makes only two Dreamliners per month, and some experts doubt that the company can hit that target in two years.
Boeing shares were up 3.1 percent at $63.91 on the New York Stock Exchange.
(Reporting by Tim Hepher in Seattle and Kyle Peterson in Chicago. Editing by Robert MacMillan)