The case for the European Union "is stronger now than ever", shadow foreign secretary Hilary Benn will declare, in a firm signal of his support for the referendum "in" campaign.
Brexit would leave Britain less able to deal with global challenges such as the migrant crisis and climate change, he will say, mocking Eurosceptics for seeking to "close the doors and wish that the rest of the world would go away".
Mr Benn - who campaigned against British membership at the time of the last public vote in 1975 - will say it had become clear over the subsequent decades that it was in fact very much in the national interest.
Labour leader Jeremy Corbyn has made clear Labour will back continued membership despite appearing to leave the door open for backing withdrawal during the party leadership campaign.
But he has expressed major concerns about the proposed transatlantic trade deal and has been criticised by some pro-EU figures for giving only lukewarm backing to the "remain" campaign.
His intervention came as European leaders were given the latest draft of the reform deal being sought by Prime Minister David Cameron to persuade voters to stick with EU membership.
A Downing Street source denied changes to the proposals represented a weakening of the package first set out last week by European Council president Donald Tusk and including an "emergency brake" on in-work benefits for migrant workers.
Mr Tusk sent out the latest version after announcing he had cleared his schedule for talks with key EU leaders in a bid to secure agreement at the summit on February 18/19, admitting the negotiations remain "fragile".
Mr Cameron hopes to seal a final deal when leaders from the 28-strong bloc meet in Brussels to allow the promised in/out referendum to be held before the summer.
The Times reported that some elements appeared to have been diluted but the No10 source played down the significance of what they said were "relatively minor technical changes" that left the "substance" of the draft deal "unchanged".
Mr Benn, whose former cabinet minister father Tony Benn was a leading Labour opponent of EU membership in the 1970s, will say: "I have changed my view on Europe since 1975.
"I have been on a journey, not least because Britain has been on a journey too. We live in a changing world and if you look at the future challenges we face I believe the case for Europe is stronger now than ever.
"The story of Britain over the last century is one of a nation at the heart of world affairs. It is the story of a country that has been at its best when we have been outward looking and confident.
"In the 20th century we helped build the institutions that have given us the chance to make progress: the UN, EU, Nato.
"In the 21st century we cannot afford to reduce our influence or to isolate ourselves or shut the curtains and close the doors and wish that the rest of the world would go away."
The EU has been criticised for its slow response to the huge increase in the numbers arriving in Europe from Syria and other troubled countries, seeking asylum or a better life.
But Mr Benn will argue the situation would have been far worse if there had been no formal cooperation.
"The flow of refugees has put the Schengen agreement under enormous strain and has tested Europe's solidarity to the limit," he will say.
"But imagine what would have happened - what would be happening now on the continent of Europe - if the European Union did not exist.
"The fact is that in Europe, as elsewhere in the world, we not only have a moral interest in preventing conflict, stopping dangerous climate change and promoting economic development to overcome poverty in developing countries, but also a practical interest in doing so.
"The choice is very simple: either we seek to do so in cooperation with our neighbours, near and far, through bodies like the European Union and the United Nations, or we will struggle to deal with them separately.
"So we must choose between the fear that we have somehow lost our identity, our influence and our place in the world because we have chosen to be part of the European Union, and the experience that being in Europe has actually amplified, extended and increased Britain's voice in the world.
"And in so doing it has given us the best means we have of dealing with the problems we face."
Mr Tusk said the threat posed to Europe by radicalism was comparable to the situation on the eve of the First World War.
"We need to be as effective as possible in our campaign against radicalism because I feel that as a historian it is very similar to some very dangerous moments in our history," The Times reported him saying.
"You know what I mean: it is like the day before World War One."