Former Marks & Spencer boss Lord Rose claims Britain's membership of the EU saves all Britons £480m (around €650m) a year and the risk of leaving is a "leap in the dark".
Launching the Britain Stronger In Europe campaign, he attacked those who want to leave as "quitters" who are "running away" from attempts to reform the EU.
He said opting out of the EU would be a risk to the economy and membership meant Britain benefited from hundreds of billions of pounds in exports and investment.
Three million jobs in the UK were linked to Europe, he said.
Speaking at an event in central London, Lord Rose said that while he has been highly critical of the EU in the past, he wants change and not to quit, adding: "Wanting reform, however, is not the same as wanting to leave."
He said the EU was not perfect, but that membership "benefits clearly outweigh the costs" and that his campaign would reach out to every corner of the UK to make the case for staying in.
Lord Rose said: "To claim that the patriotic course for Britain is to retreat, withdraw and become inward looking is to misunderstand who we are as a nation."
In a separate interview, Lord Rose said he would campaign for Britain to stay in Europe "come what may" - even if David Cameron failed to negotiate a better deal.
But he added he believed the British prime minister would be successful, saying: "We will get some concessions from Europe. Europe does not want us out of Europe."
He said those who thought leaving the EU would solve the migrant crisis were wrong.
Campaigns
The new campaign has the support of all three living former British prime ministers: John Major, Tony Blair and Gordon Brown.
The "Out" side continues to be hamstrung by division and rivalries, with two groupings, "Vote Leave" and "Leave.EU", competing for precedence.
Speaking on Sunday, UKIP leader Nigel Farage suggested Boris Johnson could be persuaded to lead the campaign for Britain to leave the EU.
He also claimed that around half of Conservative members were in favour of leaving.
Speaking during a trip to Osaka in Japan, Mr Johnson repeatedly refused to rule out leading the campaign for Britain to leave the UK.
He told the BBC: "We want, in an ideal world, to stay in a reformed European Union but I think the price of getting out is lower than it's ever been. It's better for us to stay in, but to stay in a reformed EU. That's where I am."
Poll results have varied widely and the indications are public opinion even at this early stage is extremely volatile.
YouGov has a small lead for "Brexit" (40% leave, 38% remain), ICM shows a small lead for staying in (39% leave, 44% remain) and ComRes shows a big lead for the In campaign (36% leave, 55% remain).
