"It is with humility, pride and a great sense of duty that I accept the privilege and the great responsibility of leading our party and changing our country," said the new prime minister.
Brown has already been running Britain's booming economy for a decade, as Chancellor of the Exchequer and Blair's most senior cabinet member, reports CBS News foreign correspondent Elizabeth Palmer.
Since 1997, when he won a landslide election victory, Blair ran a largely popular and effective government until the invasion of Iraq.
Blair volunteering British troops earned him a standing ovation in Washington but a new nickname at home: Bush's Poodle.
With his popularity in freefall, Blair accepted it was finally time to hand over to Brown, even though it was clear the two men had grown apart — Brown, the sober Scot, uncomfortable with Blair's slickness and spin.
In the run-up to taking office, Brown has worked hard to keep expectations low. He's offered no promises because he knows his first task is to regain the public confidence that Blair had lost.
After that, Brown with turn his attention overseas, where the relationship with America is likely to cool a little.
"It's always been Britain's tradition to stay close to the White House, but I think we'll see a certain caution after the disaster of the Iraq War," said Polly Toynbee, a political columnist of The Guardian.
Brown inherits the fallout of the Iraq War and the rest of Blair's legacy on Wednesday, when he becomes officially Prime Minister Gordon Brown.