Chancellor Gordon Brown has warned that everyone in the United Kingdom would suffer economically and culturally if Scotland voted for independence.
Mr Brown told the Scottish Labour Party conference that the economic futures of Scotland and the rest of the UK are inextricably linked.
UK links must be kept for "solidarity" in the "interdependence" age, he said.
The Scottish National Party (SNP) said Mr Brown was responsible for "Scottish economic underperformance".
Mr Brown used his question and answer session at the conference to attack Labour's opponents.
Earlier, writing in the Daily Record newspaper, he pointed to links between Scotland and the rest of the UK by saying: "Two-and-a-half million people in Scotland have a family in England."
He added: "Almost one in six Scots make their home south of the border and 400,000 people who live in Scotland are English-born."
In his conference session, he claimed that Britain is a model for how countries can co-operate together.
Mr Brown said: "The 21st Century is going to be characterised by interdependence."
He added that those who "believe in solidarity across borders and across countries know that to sever links with countries when these links are so close is not only bad for economics, it is bad for the solidarity that should exist across borders and across countries in this world".
SNP leader Alex Salmond said Labour in Scotland were "incapable of running their own campaign without remote control from their London masters".
He said Mr Brown's "Scottish economic underperformance" included a "10-year growth rate which has been behind the UK" and Scottish families with "a significantly lower income than families elsewhere in the UK.
"It is clear that the chancellor is more interested in getting the keys to number 10 than success for Scotland."
BBC political correspondent Norman Smith said Mr Brown's comments come amid mounting fears within the government that the Scottish National Party could be victorious in next May's elections to the Scottish parliament.
On Friday, Prime Minister Tony Blair urged Labour to defend Scotland from the "constitutional nightmare" of an SNP government.
Speaking at the conference, the chancellor said Labour had to "expose" what opponents "are up to".
He said: "The Conservatives don't care about the union and about Britain. They are fighting a policy of English votes for English laws.
"The Liberals have a shopping list that doesn't add up at any point.
"And the Nationalists continue to practice a politics of grudge and grievance and we have got to expose it."