The action comes exactly two years after David Cameron returned from talks in Brussels to launch the campaign to keep the UK in the EU.
The advertising blitz aims to promote the benefits of a close relationship with the EU in the run up to a vote on whether Britain should remain in a European customs union.
The campaign is being run by Best For Britain, a group part-funded by George Soros’s Open Society Foundations.
Best for Britain chief executive Eloise Todd said: “There will be some billboards but there’ll also be a lot of digital spending too.”
She added the group was “taking a leaf” from the Leave campaign.
The group has already declared donations of around £1.2m, including £500,000 from George Soros’s Open Society Foundations and £172,000 from an online fundraiser.
The publicity will target voters in the Midlands and north.
Although previous anti-Brexit campaigns have failed to gain traction, facing accusations they were seeking to undo a democratic vote, Best for Britain has more than 500,000 people on the group’s mailing list. Open Britain, formed out of the pre-referendum Remain campaign, has a similar number of Facebook followers.
An email campaign late last year helped the government lose a key vote in December to give parliament a legal guarantee to veto any final Brexit deal.
Anti-Brexiteers argue Prime Minister Theresa May lacks a majority in the house of Commons for taking Britain out of a customs union with the EU, and Tory rebel Damien Green told the BBC on Monday the government should release its impact assessments on Brexit.
Emily Thornberry, shadow foreign secretary, said on Sundaysome form of customs union was the only way to avoid a hard border with Ireland.
And although the Labour party maintains its stance that the customs union is a “viable end position”, the Financial Times reports shadow ministers are thought to be edging towards backing the UK to stay in the customs union after Brexit.
An amendment to the customs bill will look to keep the UK in the EU customs union, and MPs are expected to vote on amendments in March.
Francis Grove-White, deputy director of Open Britain said: “It’s an absolutely critical moment”.
But George Soros wants to go even further than winning in parliament. He predicts the economic impact of leaving the bloc “will become much more painfully obvious in the next six months”.
He wants to push public opinion to “a tipping point in the next six to nine months” before MPs vote on the deal negotiated by Mrs May.