Air New Zealand's flight has left for Chicago, the longest non-stop service in the airline's network with passengers facing about 15 hours on the plane.
The flight left from Auckland Airport about 5pm.
Air New Zealand's chairman Tony Carter said that any new route was important but "being our longest route is even more significant," he said.
The airline's second longest route - Houston - had been a success and Chicago gave it access to another important part of the United States.
Tourism Minister Kelvin Davis, who is on the inaugural service said the non-stop flight would be a boost to the visitor industry.
In 2017 over 330,000 Americans visited New Zealand, spending nearly $1.3 billion across the country. These numbers are projected to grow, with visitors expected to contribute over $2.3 billion to the New Zealand economy by 2024.
"The Auckland to Chicago flight will make it easier than ever for visitors from our third-largest visitor market to get a taste of New Zealand, and for kiwis to experience one of the most vibrant cities in the world,said Davis.
"We want a tourism industry that delivers productive, inclusive and sustainable growth. With nearly 60 per cent of American visitors travelling outside of the peak seasons, this new route will spread the benefits of tourism across the year and help to achieve our tourism goals."
In addition to tourism links, the United States is New Zealand's fourth-largest trading partner and one of the largest sources of direct investment.
The 13,200km flight back to Auckland will take even longer - because of prevailing headwinds - and could take about 16 hours.
Ultra long haul travel is growing in popularity as passengers enjoy the convenience of stop overs at airports.
While about 2000km short of the world's longest service - Singapore Airlines' flight from its base to New York, the Air New Zealand service is in the top 20 longest.
The flight will be the longest to touch down at O'Hare International Airport, the sixth busiest in the world.
During the past six months, airline operational staff have been war gaming "virtual flights" over the route to see how weather will affect the service, especially heading southbound.
The flight needed new approval of the Civil Aviation Authority and the airline and unions negotiated a new agreement for crew because of the duration of the flight. There will be four pilots and 10 cabin crew on the Chicago flights which run three times a week.
Chief flight operations and safety officer David Morgan has said Chicago posed challenges in winter with snow and ice, and in summer, thunderstorms and intense heat can be disruptive.
"It's not a particularly significant flight time and length going up because of the tail wind, but the challenge is coming back again," says Morgan.
The Dreamliners used on the Chicago route are the latest to be delivered to the airline and are fitted with new generation Trent TEN engines which haven't caused airlines problems and are not subject to the extra checks and range restrictions imposed on "Package C" engines.
• The Herald is travelling to Chicago courtesy of Air NZ