Neil Kinnock, Margaret Beckett, David Blunkett, Jack Straw and Hilary Benn have signed a letter in support of the Britain Stronger in Europe cross-party campaign group.
The five supported Britain leaving Europe in the referendum of 1975. Now, however, they believe an exit would put the country's economy and security at risk.
"Leaving would be a huge risk to prosperity, security and the opportunities of future generations," they said, in an open letter published in the Sunday Mirror. "The EU is not perfect and improvement is always worth making, but the benefits far outweigh the costs."
"In the 1975 referendum we all campaigned against remaining in what is now the European Union. Now, and for a long time past, it has been clear Britain is stronger, safer and better off than we would or could be if we pulled out."
The Stronger in Europe campaign said the support was "hugely significant".