Ms Christina Romer, who chairs the White House Council of Economic Advisors (CEA), will step down next month, Xinhua reported.
After her resignation, effective September 3, Romer will resume her position as professor of economics at the University of California, Berkeley, where her son will be starting high school in the fall, the White House said in a statement on Thursday.
As CEA chair, Ms Romer is one of the key economic advisers who meets President, Mr Barack Obama, on almost daily basis to help chart the response to the deepest recession since the Great Depression.
She also has been a forceful and tireless advocate of additional measures to support the recovery and help the unemployed, including additional fiscal relief to state governments to prevent the layoffs of hundreds and thousands of teachers.
"Christy Romer has provided extraordinary service to me and our country during a time of economic crisis and recovery," said Mr Obama.
"The challenges we faced demanded more of Christy than any of her predecessors, and I greatly valued and appreciated her skill, commitment and wise counsel."
After quitting CEA, Ms Romer would continue to provide guidance as a member of the Economic Recovery Advisory Board, a panel of non-government experts who monitor the economic recovery and offer ideas.
There was no immediate word on Ms Romer's successor.
Ms Romer is the second person in Obama's economic team to announce resignation. Peter Orszag, former director of the White House Office of Management and Budget, left last month.