The Qatar Airways flight between Edinburgh and Doha will run five days a week from May 28.
VisitScotland said it will bring in about £33 million in projected revenue in the first year and £86 million after three years.
It is one of six new direct routes starting this month connecting Scotland to Philadelphia, Chicago, Zurich, Verona and the Dominican Republic.
The flights have been highlighted as VisitScotland attempts to attract more visitors and businesses to set up links with the country at the IMEX tourism trade show in Frankfurt.
The conference sees businesses from the tourism industry meet airlines and travel companies, and VisitScotland hopes events such as the Commonwealth Games and the Ryder Cup can lead to further opportunities.
VisitScotland's delegation includes a number of hotels, conference centres and marketing groups.
Neil Brownlee, head of the business tourism at VisitScotland, said: "Scotland is excelling in business tourism, evidenced by the wealth of major investments happening throughout the country including accommodation, venues and major new flight routes.
"We are looking forward to communicating the importance of doing business in Scotland to over 9,000 buyers at the event.
"With the Commonwealth Games, Ryder Cup and over 800 Homecoming events, 2014 is set to be a massive year for Scotland and this delivers great opportunities for not only business tourism, but for the whole of the Scottish economy.
"It's imperative we make the most of this once-in-a-generation opportunity and this year's IMEX is the perfect place to do just that."