Conservative minister Ken Clarke has joined forces with Liberal Democrat Danny Alexander and Labour's Lord Mandelson to warn that leaving the EU would be an "historical error".
The politicians insisted the UK should work to reform the organisation from within rather than walking away.
Mr Clarke, regarded as the sole Conservative europhile in the Cabinet, said: "David Cameron has already shown what can be achieved in Europe through strong, determined leadership.
"We earn our living in a globalised economy and a world in which nations are interdependent in tackling global and regional problems.
"We can help to promote our own interests best by reinforcing our role as a leading nation in the EU."
More top news
Overhaul of NHS would include workplace weight-loss schemes with money and shopping voucher prizes.
It is a wet and windy picture for many tonight, with the worst in the northwest.
Singer Jamelia told ITV News Ukip "are knobs" as she arrived at tonight's Mobo Awards, saying they "want me to go home".