National leaders, meeting as the European Council, would be reduced to consultative, second chamber role similar to the House of Lords.
Nigel Farage, the leader of Ukip, said that Mrs Reding had revealed the true choice for British voters to make at polling stations.
"For people in power in Brussels that is the only choice on offer, no reform just a United States of Europe. On 22 May the British people must ask themselves if they want this and vote accordingly," he said.
"I am sure people will say no to this centralist fanaticism."
Mrs Reding's comments illustrate the growing gulf between a Europe committed to "ever closer union" and Britain, which is pushing to reduce the EU's powers.
"We assume Britain's leaving the EU so we don't even bother thinking about British sensitivities at the moment," said an official.
While Britain may have been written off, concern is mounting because hostility has reached unprecedented levels across continental Europe and anti-EU parties are leading the polls in France, the Netherlands and Greece.
Senior EU figures, such as Mrs Reding, want the European elections in May to move beyond debates over eurozone austerity by embracing a grand vision of Europe.
"This debate is moving into the decisive phase now. In a little more than four months' time, citizens across Europe will be able to choose the Europe they want to live in," she said.
"There is a lot at stake. The outcome of these elections will shape Europe for the years to come. That is why voting at these elections is crucial.
This will be our best weapon against the Eurosceptics: to explain to our citizens that their vote really matters."
In the run up to the springtime pan-European vote, the EU is gearing up to mount an unprecedented campaign for the hearts and minds of voters.
Speaking in Athens, José Manuel Barroso, the commission president, signalled that the EU would use the centenary of World War One to warn that Euroscepticism, far-Right and populist anti-European parties could bring war back to Europe.
"No other political construction to date has proven to be a better way of organising life to lessen the barbarity in this world," he said.
"It is especially important to recall this as we will commemorate this year the start of the First World War. We must never take peace, democracy or freedom for granted. It is also especially important to remind this as in May the peoples of Europe will be called to participate in European elections."
The attempt by Mr Barroso and Mrs Reding to raise the stakes in the EU elections have not been well received by all governments.
"Federalist hyperbole about a United States is the opposite of helpful to the majority of countries who want a reformed EU to work better," said a European diplomat.