Yellen, 67, currently the Fed's vice chair, has been an influential proponent of the Fed's extraordinary measures to revive the battered American economy, even though interest rates are already close to zero.
When Yellen succeeds Ben Bernanke, whose second four-year term as Fed chairman ends on January 31, she will become the first woman to run the Fed in its 100-year history.
Senators voted 56 to 26 in her favour, with many missing the vote because of inclement weather. Eleven Republicans broke party ranks, voting to support Yellen, described by President Barack Obama as one of America's most respected economists.
"As one of our nation's most respected economists and a leading voice at the Fed for more than a decade and Vice Chair for the past three years, Janet helped pull our economy out of recession and put us on the path of steady growth," he said.
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Pelosi said Yellen will lead the Federal Reserve with an extraordinary level of discipline, determination, and expertise on America's economy.
US Treasury Secretary Jacob Lew said with many years of experience in economics and at the Federal Reserve, Yellen is a proven leader who will assume the vast responsibilities of this position with a steady hand.
"Janet is not only enormously qualified to take on this role, she is also widely respected for her keen mind, sound judgement and independence. At the Federal Reserve, she has been a vital and often prescient voice," he said.