At the time of death he was President Barack Obama's special envoy to Afghanistan and Pakistan.
Mr Obama called the 69-year-old, who was known for bringing warring leaders to the negotiating table, a "true giant of American foreign policy".
Mr Holbrooke was meeting Secretary of State Hillary Clinton at the US state department on Friday morning when he collapsed.
He was rushed to the US capital's George Washington University Hospital, where he underwent a 21-hour operation to repair a tear in his aorta - the largest artery in the human body, which carries oxygenated blood from the heart.
Mr Holbrooke's death comes as the Obama administration prepares to make public its latest review of US policy in Afghanistan and Pakistan later this week.
