For Brown, who for 10 years has controlled the national finances as chancellor of the exchequer, it is the culmination of a long - and reportedly frustrating - quest for the top job.
Brown's devotion to fiscal "prudence" and his commitment to increasing aid to Africa are well known, but questions remain to be answered about what he intends to do in Iraq and more generally about his foreign policy goals.
British troop numbers in Iraq have rapidly fallen through 2007 and soldiers are now stationed on the fringes of the southern city of Basra.
Blair has left his successor an option to call back more of the remaining 5,500 personnel by 2008 - an opportunity likely to be grasped by a leader with a national election to call before June 2010.
"His hands, whilst not quite clean, are certainly not sullied," said Alasdair Murray the director of CentreForum, a liberal think-tank. Brown can "portray it as Blair's war and differentiate himself."
Brown may sanction a future inquiry on Iraq, similar to the U.S. Study Group, British media have reported. Britain has to "admit where we make mistakes," Brown told a recent rally, referring to the war.
"Blair always had an eye on building up that currency called influence," said Neil O'Brien director of the London based Open Europe think tank. "Brown is likely to be more ready to put his foot down and say no."
Brown and Blair were elected to Parliament in 1983, shared an office and rose rapidly to prominence in the party. It has been widely reported - but never confirmed - that the two men agreed over dinner in 1994 that Brown would not oppose Blair as a candidate for the Labour Party leadership following the death of John Smith.
The other part of the reported deal was that if Blair became prime minister, as he did in 1997, he would step down at some point to give Brown a shot at the top job.
Brown was unopposed in the Labour Party leadership election to choose Blair's successor.
Labour lawmakers and activists placed their trust in Brown to revive party fortunes after more than a year of trailing the opposition Conservatives in opinion polls.
Once Blair has tendered his resignation to Queen Elizabeth II at Buckingham Palace, Brown was to be summoned to the queen's private quarters to be formally confirmed as prime minister during a closed-door audience.
To officially become British chief, the queen must invite the leader of the largest party in the House of Commons to form her government. He was to be the 11th politician - Winston Churchill was the first - she has invited to lead her government.
Blair was heading to northern England - where he is expected to tell local officials he plans to quit entirely as a lawmaker to take a potential new role in the Middle East.
Brown enters office a day after claiming one more vote in the House of Commons.
Quentin Davies, a Conservative lawmaker for 20 years, resigned from the party Tuesday to join Labour.
Davies accused Conservative leader David Cameron of have no clear policies or principles, and praised Brown as "a leader I have always greatly admired, who I believe is entirely straightforward, and who has a towering record, and a clear vision for the future of our country which I fully share."
Blair called a meeting of local party officials in Sedgefield, northern England, for late Wednesday planning to tell them he will quit as their representative in the Commons if offered a role as envoy to the Quartet on Mideast peace - sparking a special election for his seat.
"If he gets the Middle East job, he will resign," said John Burton, Blair's political representative in the town.
While Brown in moving up the ladder, he won't be moving house. He, his wife Sarah and two young sons have been living in the private quarters at No. 10, the prime minister's official residence, while Blair's larger family has been living next door in No. 11, Brown's official residence.
Is it possible for aggrieved nations to gain favorable international tribunal rulings against the US that force it to pay a price for its crimes?