The Turkish Airlines flight has been described as "historic" and is said to have the potential to promote greater global connectivity and encourage more airlines to leave from Edinburgh airport.
The Turkish city spans two continents and is often described as "the gateway to the east".
Such direct routes are "crucial" due to "increased taxation and growth constraints in the UK", according to airport chief executive Gordon Dewar.
The SNP has seized on today's flight announcement to renew its call for devolution of air passenger duty to make it "more competitive" and attract more airlines to Scotland.
Mr Dewar said: "This is a significant development for Edinburgh airport and the wider city.
"It sets the tone for the new ownership of Scotland's premier airport - greater global connectivity and working with major airline partners such as Turkish.
"Connectivity guides everything we do and this new route is doubly exciting because of the onward connection possibilities Istanbul offers.
"We're committed to continuing to play our role in the Scottish economy by linking the capital to as many destinations as we can.
"As we face increased taxation and growth constraints in the UK, it is crucial that we secure further direct routes across Europe and beyond."
New owners Global Infrastructure Partners (GIP) bought Edinburgh airport last month for £807 million after the Competition Commission forced former owners BAA to sell up.
Infrastructure Secretary Alex Neil said: "The Scottish Government is determined to improve our international air connections with key global markets and this new service to Istanbul is a significant step forward in that respect.
"As well as providing direct access to Istanbul and the tourism and business opportunities offered by such a dynamic city, this service is also a gateway to worldwide destinations such as China and India.
"I am delighted to welcome Turkish Airlines to Scotland.
"As one of the largest airlines in the world, the fact they have chosen to fly from Edinburgh is an indication of the quality and calibre of airline Scotland is attracting and a major success story in our drive to maximise the economic benefits which direct air connections bring."
SNP MSP Colin Keir, whose constituency includes the airport, said: "If air passenger duty was more competitive and devolved to Holyrood, we could be seeing a lot more airlines choosing to invest in Scotland."
Temel Kotil, chief executive of Turkish Airlines, said: "We are very happy to start flying from Edinburgh, the capital city of Scotland, to more than 200 destinations around the world from today."
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