The Solar Impulse 2, piloted by Swiss explorer and psychiatrist Bertrand Piccard, lifted off just before sunrise to cheers and applause.
It will head for the San Francisco Bay area, some 4,000 kilometers (2,500 miles) away. And because the plane travels at about the same speed as a car, the Hawaii-California leg will take about 62 hours to complete.
"It's a very stable weather window," Solar Impulse spokeswoman Alexandra Gindroz said.
That forecast will be a relief for Piccard and his business partner, Swiss engineer Andre Borschberg, who take turns flying the plane solo.
After all, it's the weather -- particularly the sun -- that ultimately decides the schedule of this journey, even with dozens of engineers and experts monitoring the plane's every move.
The solar plane looks like a giant high-tech dragonfly, with the wingspan of a Boeing 747. But because it weighs only about as much as an SUV, it requires near-perfect conditions to fly.
"Nobody's done this before," managing director Gregory Blatt said. "There's no guidebook. There's no best practice."
The team has learned this the hard way.
Rolling with the punches
The Solar Impulse 2 was originally supposed to land in Abu Dhabi, where it started its journey in March 2015, by the end of last summer.
But a series of frustrating weather delays in China slowed progress for weeks, followed by an unexpected diversion to Japan, where the aircraft was damaged on the tarmac by a storm.
Still, the pilots and their team of more than 100 pushed onward, repairing the aircraft and preparing it for what they called "the moment of truth" -- the Pacific crossing to Hawaii.
It was a moment of human achievement. For almost five days and five nights, Borschberg piloted the plane wearing an oxygen mask as it climbed up 8,000 meters (5 miles) high during the day, its solar cells soaking up enough energy to propel the aircraft through the night.
'We made a mistake'
While Borschberg set a new record for the solo flight, clocking in at 117 hours and 52 minutes, a chain of events caused the batteries to overheat.
It was only after he landed that the team discovered how bad the damage was.
"We made a mistake with our batteries," Piccard said after the plane touched down in July. "It was a human mistake."
And a mistake that took more than nine months to fix.
Back in the air
Fast forward to this spring, and the Solar Impulse 2 has new batteries, a new cooling system that can be manually operated by the pilot, and $20 million in fresh funding to keep the mission up and running.
The engineers and pilots flew more than eight training and maintenance flights over the past few months, and the plane has been performing remarkably well, Blatt said.
While the team is pumped up and feeling confident, Blatt said he recognizes the challenges ahead, including tricky springtime weather over the U.S. mainland.
After several stops in the United States, the pilots hope to cross the Atlantic Ocean, and then Europe or northern Africa.
They plan to return to the Middle East by late summer, completing a 35,000-kilometer (27,000-mile) trip around the world.