In a bravura 65-minute performance, delivered without notes, Mr Miliband won warm applause from his audience in Manchester and the approval of commentators outside the hall as he called on Britons to come together in the fight to overcome the economic downturn.
He made no bones about stealing his One Nation slogan - first used by Conservative prime minister Benjamin Disraeli - from the Tories, insisting that David Cameron had forfeited his right to claim that "we are all in this together" because of the way he has governed since 2010.
Denouncing Mr Cameron's Government as a "miserable shower" who had allowed state borrowing to rise, destabilised the NHS and cut taxes on millionaires while increasing them for pensioners, the Labour leader said: "If the medicine isn't working, change the medicine... (and) change the doctor too."
In a speech which was light on policy proposals, Mr Miliband put forward plans to end the requirement on businesses for quarterly reporting, in order to encourage long-term investment and planning. He challenged the banks to separate their retail and investment arms by 2015 or be forced to by law.
But it was an address devoted to introducing Mr Miliband to voters as a person and to getting across his vision of how a Labour administration would govern under his leadership.
Drawing an implicit comparison with Mr Cameron's privileged Home Counties upbringing and Eton education, the Labour leader recalled his childhood as the son of Jewish refugees from Nazism and his schooldays in a north London comprehensive.
"It is this upbringing which has made me ... who I am - a person of faith, not of religious faith, but a faith nonetheless," he said.
"Here is my faith. I believe we have a duty to leave the world a better place than we found it. I believe we cannot shrug our shoulders at injustice and just say that is the way the world is, and I believe we can overcome any odds if we come together as people."
Britain showed the One Nation spirit when it came together to fight Hitler's Germany in the Second World War and to rebuild the war-battered country under Labour PM Clement Attlee.
And in this summer's Olympic and Paralympic Games, "we succeeded because we came together as a country, we worked together as a country, we joined together as a country. That is why we achieved more than we imagined possible".
Mr Miliband told delegates: "I didn't become leader of the Labour Party to reinvent the world of Disraeli or Attlee but I do believe in that spirit, that spirit of One Nation.
"One Nation: a country where everyone has a stake. One Nation: a country where prosperity is fairly shared.
"One Nation where we have a shared destiny, a sense of shared endeavour and a common life that we lead together.
"That is my vision of One Nation, that is my vision of Britain, that is the Britain we must become."
He denied his approach meant ducking difficult decisions. And he made clear that - despite pressure from unions and the left - he would not be able to reverse all of the coalition's cuts if he came to power, and would continue to support the public sector pay freeze during this Parliament.
But he insisted a Labour administration would ensure that "those with the broadest shoulders will always bear the greatest burden".
Labour must not be "the party of one sectional interest", but must represent the private and public sectors, small businesses as well as workers, and the "squeezed middle" as well as those in poverty.
But Mr Miliband also sought to draw a line under New Labour, which he said was "too silent" about the responsibility of those at the top and "too timid" about the accountability of the powerful.
Mr Miliband said he "understood" voters who turned their backs on Labour in 2010 amid the financial crisis and gave Mr Cameron "the benefit of the doubt".
But he said the coalition had delivered "the longest double-dip recession since the war" and branded Nick Clegg's Liberal Democrats "shameful" for agreeing to cut the top rate of income tax from 50p to 45p.
"This Prime Minister said we are all in it together," said Mr Miliband. "Don't let him ever tell us again we're all in this together.
"You can't be a One Nation prime minister if you raise taxes on ordinary families and cut taxes for millionaires.
"You can't be a One Nation prime minister if all you do is seek to divide the country between north and south, between public and private, between those who can work and those who can't work."
Reeling off a list of Government mishaps, from the pasty tax to chief whip Andrew Mitchell's "plebgate" and Mr Cameron's texts to Rebekah Brooks, Mr Miliband asked: "Have you ever seen a more incompetent, hopeless, out-of-touch, U-turning, pledge-breaking, make-it-up-as-you-go-along, back-of-the-envelope, miserable shower than this Prime Minister and this Government?"
Bookmakers William Hill instantly slashed the odds on Mr Miliband leading Labour into the election from 4/11 to 2/9 and installed him as 10/11 favourite to be the next prime minister.
And union leaders, who started the week with strong criticism, joined a chorus of praise from supporters. Unite general secretary Len McCluskey described the speech as a "tour de force" and GMB leader Paul Kenny said it gave "a glimpse of what a fantastic prime minister he would make".
Tony Blair's former communications chief Alastair Campbell said Mr Cameron would be "worried" by the speech, while ex-Labour leader Lord Kinnock said: "It was brilliant in all respects... What he's doing is manifesting the strengths that made me want him to be leader."
But Conservative Party chairman Grant Shapps said: "To prove he is credible, Ed Miliband had to do more than give a speech to rouse the Labour Party faithful; he had to show that he had learned from the mistakes that Labour made in office.
"Instead he failed to back our welfare cap, failed to back our immigration cap and still stands for more spending, more borrowing and more debt - exactly what got us into this mess in the first place.
"Sadly, Labour isn't learning."