She plans to retire early next year, a statement from the bank said.
Pianalto, 59, called it "an honor" to serve as the regional bank's president and to participate in the Federal Open Market Committee "during this extraordinary period in our country's economic history," Pianalto said.
The committee, which makes key decisions about interest rates and the growth of the U.S. money supply, has sought to stimulate the U.S. economy since the financial crisis by buying Treasury securities and mortgage-backed bonds every month since November 2008.
It recently announced it would begin gradually scaling back on its monthly purchases -- a statement Pianalto reiterated in a speech Wednesday.
"I have no immediate plans beyond continuing my involvement in civic and non-profit activities," Pianalto said in her announcement.
Pianalto serves on the boards of many regional non-profit organizations, including the Rock and Roll Hall of Fame and Museum.
"I will not consider any opportunities until my successor is in place," Pianalto said, promising to stay "actively engaged" in the Fed until her successor is chosen.
The Cleveland Fed's board has formed a search committee to appoint a successor. The appointed is expected to be made "in early 2014," the bank said.
"We will miss her thoughtful insights and leadership across a broad range of issues, including monetary policy, payments policy and community development," Fed Chairman Ben Bernanke said in a statement.
The Cleveland Fed is one of 12 regional banks in the U.S. Federal Reserve system. The district is composed of Ohio, western Pennsylvania, eastern Kentucky and the northern panhandle of West Virginia.
Pianalto, who was born in Italy, is the longest-serving regional Fed president. She was named to lead the regional bank in February 2003, 20 years after joining the Cleveland Fed.
In her 10-year presidency, Pianalto never dissented from an FOMC monetary-policy decision.
Notable deaths of 2014 [PHOTOS]