MORE: McDonald's unveils new global menu for West Loop HQ
Part of the nine-story complex features a McDonald's restaurant with menu items from all over the world.
It relocated from Oak Brook and is now at the spot where Oprah's Harpo Studios used to be.
The new headquarters takes up a full block from Randolph Street to Washington Boulevard and Carpenter to Aberdeen streets.
The new headquarters will house the flagship Hamburger University.
"McDonald's has been a top global innovator for more than half of a century because they recognize the key to success is access to the world's best talent, technology and transportation networks," Mayor Emanuel said. "This new global headquarters represents a renewed commitment to that strategy and I'm proud to welcome them home to the city of Chicago."
McDonald's had previously been headquartered in Chicago from 1955 to 1971 before moving out to Oak Brook.
"Our move back home to Chicago is about more than a building - it's symbolic of our journey to transform our brand and become more closely connected with our customers," McDonald's CEO Steve Easterbrook said. "Our new location enables us to better listen, learn and engage with our customers whilst providing a modern, worker-friendly headquarters that fosters collaboration and re-energizes employees. We are thrilled to join the West Loop and add to the vitality of this community."
The headquarters will have displays of Happy Meal toys and vintage memorabilia throughout the building, as well as a tribute wall to McDonald's leaders..