A statement issued by the US-based group late on Tuesday said: "Our hearts are broken by this turn of events".
It was not immediately clear why the registration was revoked.
Since 2012, Mercy Corps has conducted from Turkey one of the largest aid operations in Syria, assisting up to half a million civilians each month.
It has also provided a range of social services and other emergency assistance in Turkey, reaching about 100,000 Syrian and Turkish people in 2016 alone.
Mercy Corps' statement said its operations inside Syria would continue.
"Our priority right now is to limit any adverse effects our departure from Turkey may have on the innocent men, women and children who depend on our assistance."
"We continue to seek a dialogue with Turkish authorities in an effort to obtain permission to resume our operations in Turkey as soon as possible. We remain hopeful that the government of Turkey will allow us to return to serve those in critical need," it added.
Turkey has opened its doors to more than 2.91 million refugees since the uprising against Syria's President Bashar al-Assad began in 2011, and has also served as a hub for deliveries of humanitarian aid to Syria.
Turkish officials have so far not told Mercy Corps why its registration was revoked.
But in November the government closed hundreds of non-governmental groups it accused of being linked to terrorist organisations or acting against national security, as part of a crackdown launched after an attempted military coup in July.
A spokeswoman for Mercy Corps, Christine Bragale, said she could not speculate on the reason for the Turkish government's decision, but stressed: "We have every confidence in the impartiality and integrity of our operation."
US state department spokesman Mark Toner told the Washington Post that it was aware of the situation with Mercy Corps, which he called a "valuable partner".
"We have informed the government of Turkey of our concerns regarding Mercy Corps' closure and the impact it will have on their ability to provide critical humanitarian assistance to vulnerable populations," he said.
The aid organisation Mercy Corps says Turkey has revoked its registration, forcing it to stop operations that help hundreds of thousands of Syrians.