The expedition is to set out one day late, once a customs official arrives in Hawaii and boards the ship.
Researchers will dive around an uninhabited Pacific island where they believe Earhart crashed in 1937.
Amelia Earhart was the first woman to fly solo across the Atlantic, in 1932.
On 2 July 1937, Amelia Earhart and and her navigator Fred Noonan
took off from Papua New Guinea in their Electra 10E aircraft, en route to Howland Island.
Many experts think a navigational error caused the pair to run out of fuel over the sea. They were never seen again.
They were three-quarters of the way through an unprecedented circumnavigation of the globe around the Equator.
On 3 July, the USS Colorado departed from Hawaii in search of Earhart and Noonan.
The current expedition, which is costing more than $2m (£1.3m), is being led by Ric Gillespie, executive director of the International Group for Historic Aircraft Recovery (Tighar).
He has spent almost a quarter of a century advancing an alternative hypothesis, correspondents say.
He believes Earhart and Noonan crash-landed on the uninhabited Pacific island of Nikumaroro, where they survived for a time before finally succumbing to hunger, thirst or injury.
Over the next three weeks, Mr Gillespie and his team will deploy robots equipped with sonar and high-definition video cameras to search the waters off the island for clues.
"What we're hoping for is to come back with good imagery, photographs, of wreckage that's conclusively, unquestionably pieces, at least, of Amelia Earhart's Lockheed Electra aircraft; that's the goal," he told the BBC.
Tighar has mounted several expeditions to the island in recent years - finding bones on Nikumaroro during an earlier search, but lab tests were inconclusive on whether they were human bones.
Many historians argue there is only circumstantial evidence to support the Nikumaroro island theory.
This is Tighar's 10th expedition to Nikumaroro.
"We have continued the investigation because we have been successful in finding evidence that supports the hypothesis we are testing," Mr Gillespie told the BBC.
If identifiable wreckage is found, Tighar will return with the equipment needed to recover and conserve it, he says.