The stock, which has a market value of $149 billion, was trading down more than 2% Monday. It had slid as much as 3.1% in the premarket. Shares of the Dow component are now down more than 11% since the Dow's July 15th record close, putting it among the biggest laggards in the index. It ranks third from the bottom, ahead of Cisco Systems and Travelers.
After taking the helm of McDonald's in 2015, Easterbrook led a turnaround of the company, leading the value of its stock to nearly double. His successor Chris Kempczinski, in his prior role as head of McDonald's U.S. business, worked closely with Easterbrook in efforts to turn around U.S. restaurants.
"Given Kempczinski's role as President of McDonald's USA, he was the obvious eventual successor to Easterbrook, but the timing is clearly much sooner than anticipated," Bernstein analyst Sara Senatore wrote in a note.
Kempczinski told The Wall Street Journal on Sunday he is not planning any "radical, strategic shift."
Under Easterbrook, McDonald's increasingly turned its attention to technology. U.S. locations have been receiving tech-focused upgrades, like self-order kiosks and digital menu boards. It is trying to hit $4 billion in delivery sales by the end of 2019. The company also acquired two companies this year that are trying to use artificial intelligence in drive-thrus.
But pricey store renovations, delivery commission fees and value deals led to a fraying relationship between McDonald's management and its U.S. franchisees, who formed an independent group a year ago to address their concerns. As a result of concessions made by McDonald's, relations have improved in recent months.
"This balance of relations with franchisees and shareholders, that can sometimes have differing objectives, will be paramount as Mr. Kempczinski begins his new role," Cowen analyst Andrew Charles wrote in a note.
While Kempczinski does not have any international experience at the global fast-food chain, he was president of Kraft International before coming to McDonald's.
"We are definitely surprised by the news and view Mr. Easterbrook's departure as a loss but also believe the company's strategy is on very solid footing and the McDonald's system is much more than just one man," BTIG analyst Peter Saleh wrote in a note.
Joe Erlinger, who will take over as president of McDonald's USA, is currently president of its international operated markets, which includes countries like Australia and the United Kingdom. Before taking over that role in January, he was president of high growth markets.
Piper Jaffray analyst Nicole Miller Regan downgraded McDonald's stock following the announcement.
"Our experience leads us to take a more cautionary view noting the potential lack of momentum and time involved in formalizing a new team," she said.
McDonald's last month had its first quarterly earnings miss in two years after promotions struggled to lure U.S. customers away from the competition.
The company's Chief People Officer David Fairhurst departed the company Monday.
Easterbrook's firing follows two other recent executive departures. McDonald's global Chief Marketing Officer Silvia Lagnado and Chief Communications Officer Robert Gibbs left last month.
—CNBC's Gina Francolla contributed to this report.