Mr Obama's replacement will be chosen by the Illinois governor
US President-elect Barack Obama has said that he will give up his Senate seat on 16 November.
The move has been expected ever since Mr Obama won the presidential election on 4 November.
Mr Obama's replacement as senator for Illinois will be appointed by the state's governor, Rod Blagojevich.
Frontrunners to replace Mr Obama include Illinois Congressman Jesse Jackson Jr and Emil Jones, president of the Illinois State Senate.
Tammy Duckworth, an Iraq war veteran who heads the Illinois Department of Veterans' Affairs, has also been mentioned as a possible replacement.
Whoever is chosen will have to fight a special election in 2010 to keep the seat.
"It has been one of the highest honours and privileges of my life to have served the people of Illinois in the United States Senate," said Mr Obama in a written statement.
"I leave the United States Senate and begin the hard task of fulfilling the simple hopes and common dreams of all Americans as our nation's next president," he added.