He said his resignation was prompted by the realization he could do more to promote American Indian economic development from the private sector.
Anderson plans to leave Feb. 12, when he undertakes an economic development project in connection with Harvard University's Native American Program, the St. Paul (Minn.) Pioneer-Press said Tuesday.
He had indicated earlier that he intended to stay in the post through the end of President George W. Bush's second term.
Anderson denied his decision to step down resulted from the frustration of running an agency of more than 10,000 employees or due to criticism of his decision to recuse himself from Indian gaming decisions because of ties to the gaming industry.
"It wasn't why I left," Anderson said. "I'm 52 years old, and I don't think to spend the next four years there until I'm past 55 would be a good use of my time.
"Now I think it's appropriate for me to get back to what I know best -- being an Indian businessman, and the best rib cook in America."