The route will be operated by United Airlines.
It will operate five times weekly from 23 May to 12 June, daily from 13 June to 2 September and four times weekly between 3 September and 6 October.
Flight times will be eight hours 35 minutes westbound and seven hours 45 minutes eastbound.
The Edinburgh-Chicago flight will depart Edinburgh at 10:25, arriving in Chicago at 13:00 the same day.
The return flight will depart Chicago at 18:00, arriving in Edinburgh at 07:45 the following day.
Bob Schumacher, United Airlines' managing director sales for the UK and Ireland, said: "Having recently celebrated 15 years of operations in Scotland, we're delighted to expand our schedule with seasonal non-stop service to Chicago, United's home town.
"Next year's Homecoming promotion and Ryder Cup at Gleneagles make it the ideal time to launch these flights, which will offer our customers an increased range of travel choices and opportunities."
First Minister Alex Salmond said: "By improving direct routes overseas, we can help reduce the need for travellers to make extra connecting flights via London or the continent, support tourism, trade and investment and so further strengthen Scotland's economy.
"The eyes of the world will be on Scotland in 2014 and, as we host international sporting stars at the Commonwealth Games and Ryder Cup and celebrate another Year of Homecoming, we hope to welcome visitors from across the world, not least from the United States with whom we share strong and enduring bonds."
Gordon Dewar, chief executive of Edinburgh Airport, said the new route was "a fantastic validation of Edinburgh and Scotland as a whole".
He said: "We are delighted to have played our part in developing this route with the other agencies and government departments that make up Team Scotland.
"This collaborative approach works and we look forward to bringing many more international routes to Edinburgh in the coming months."