Qatar Airways began flights to Chicago on Thursday and said the thrice-weekly service will become daily from June 15.
The Gulf carrier's arrival at O'Hare International Airport marks the airline's fourth gateway in the United States.
Chicago became destination number 126 in the airline's rapidly growing worldwide network.
Qatar Airways now operates 24 passenger flights a week between the United States and Doha - daily from New York, Washington DC and Houston and the new services from Chicago.
Qatar Airways CEO Akbar Al Baker said: "After more than five successful years of operations in North America, we are pleased to introduce Chicago as our fourth and newest US gateway and look forward to welcoming travellers from the Midwest and its catchment area to fly with us to many parts of the world and, similarly welcome visitors from around the world to this great city.
"Chicago is a key route for business and leisure travellers alike, home to the world's second busiest international airport with 70 million passengers a year."
City of Chicago Mayor Rahm Emanuel added: "Chicago is pleased to welcome Qatar Airways' world-class service to our global gateway, O'Hare International Airport.
"This new international air service creates additional economic opportunities, increases tourism to our city and strengthens Chicago's cultural and business connection to the world. This service will generate more than $200m in annual economic impact and will connect passengers from Chicago to destinations across India, Africa, the Middle East and Asia."
Aside from Chicago, New York, Washington DC and Houston, Qatar Airways' North American operations covers thrice-weekly services to Montreal.
Qatar Airways is also set to launch services to Salalah, Oman (May 22); Basra, Iraq (June 3), Sulaymaniyah, Iraq (August 20), and Chengdu, China, at a date to be confirmed.