Obama left at 1.20 pm aboard Air Force One on the first leg of the trip, a refueling stop at Elmendorf Air Force Base in Anchorage, Alaska.
The president's tenth trip to Asia aims in part to close painful chapters on two past 20th century wars in a region he sees as vital to America's future.
In Hanoi and Ho Chi Minh City, Obama will stress improving relations with a dynamic and rapidly emerging country, but one which, for most Americans, remains a by-word for slaughter and folly.
In Japan, Obama will attend a G7 summit and make history by becoming the first sitting US president to visit Hiroshima, where in 1945 then president Harry Truman dropped the world's first atomic bomb.