Emanuel delivered the news in an automated call to constituents on Monday.
"This is Congressman Rahm Emanuel. As you may have heard, President-elect Obama has asked me to be his new chief of staff and I have accepted this offer. Therefore, in the near future, I will be resigning from Congress. ... I also want you to know, it has been a privilege and an honor to serve as your representative for the last six years," he says in the taped call.
Shortly after the election, Emanuel was the first person named to join Obama's team.
A special election now must be scheduled to fill Emanuel's seat in the 5th District, and several Chicago politicians have already expressed interest in the seat.
Emanuel was elected to that seat in 2002 to replace Rod Blagojevich, who is now battling to remain the Illinois governor after being accused of trying to sell off Obama's vacated U.S. Senate seat. Emanuel has said he had no inappropriate conversations with Blagojevich about Obama's replacement.
The Associated Press contributed to this report.