"Over the past two and a half years, George Mitchell has worked as a tireless advocate for peace as the U.S. special envoy for the Middle East," President Obama said in a statement. "His deep commitment to resolving conflict and advancing democracy has contributed immeasurably to the goal of two states living side by side in peace and security."
In his letter of resignation, Mitchell said, "I strongly support your vision of comprehensive peace in the Middle East and thank you for giving me the opportunity to be part of your administration. It has been an honor for me to again serve our country."
Secretary of State Hillary Clinton asked that Deputy Middle East Envoy David Hale be acting envoy, and Obama said he has "every confidence" in Hale's carrying on Mitchell's efforts to achieve peace in the Middle East.
Mitchell did not indicate why he was resigning, except to say that when he accepted the post, "my intention was to serve for two years."
As Mitchell returns to private life, he leaves behind a "proud legacy of dedicated public service and the country owes him a debt of gratitude for his extraordinary commitment," Obama said.
Clinton said Mitchell "represents the best traditions of American diplomacy."
From his work in the U.S. Senate representing Maine to helping to broker peace in Northern Ireland to his diplomatic assignments in the State Department, Mitchell's work "brought peace and increasing prosperity to millions of people around the world and made our own country stronger and more secure," Clinton said.
"All of us at the State Department will miss his steady leadership and wise counsel," she said, "and we will carry forward his commitment to pursue a comprehensive peace in the Middle East."
Mitchell's resignation comes ahead of a major week for the administration and its foreign policy. Obama is scheduled to give what has been billed as a key address on the Middle East Thursday. The White House also will host Israeli Prime Minister Binyamin Netanyahu and will welcome King Abdullah II of Jordan at the White House.
Notable deaths of 2014 [PHOTOS]