Jude Law, Keira Knightley and Benedict Cumberbatch are among stars who have signed a letter saying Brexit would "damage" the creative industry.
Almost 300 actors, musicians, writers and artists are backing calls for the UK to stay in the EU.
They say "vital EU funding" and work across borders has been key to projects from galleries to blockbusters.
But House of Cards author Lord Dobbs said British success in the industry was "not because of the EU".
Among others backing the letter are actors Bill Nighy, Chiwetel Ejiofor, Sir John Hurt, Sir Patrick Stewart and Thandie Newton, architect Richard Rogers, artist Tracey Emin, author John le Carre, comedian Jo Brand, fashion designer Vivienne Westwood, director Richard Curtis and writer Philip Pullman.
'Shouting from the wings'
The letter, organised by the Britain Stronger in Europe campaign, says: "Britain is not just stronger in Europe, it is more imaginative and more creative, and our global creative success would be severely weakened by walking away."
It adds: "Leaving Europe would be a leap into the unknown for millions of people across the UK who work in the creative industries, and for the millions more at home and abroad who benefit from the growth and vibrancy of Britain's cultural sector."
"We believe that being part of the EU bolsters Britain's leading role on the world stage. Let's not become an outsider shouting from the wings."
The Stronger In campaign says that more than 2.2 million people are employed in the UK's creative industries and digital sector.
It argues that the creative and digital industries export billions of pounds of services to the EU and are among the fastest-growing sectors of the UK economy.
Prime Minister David Cameron met some of the stars campaigning for Remain at a visit to the famous Abbey Road studios in London, with former Labour culture secretary Tessa Jowell.
Alan Johnson, chair of the Labour In for Britain campaign, said leaving the EU would mean higher tariffs on exports and digital and creative industries were "better off with the UK in EU" with access to the single market.
But speaking in a personal capacity, the Conservative peer and author Lord Dobbs, said: "Our creative industries are booming because of the talent that is in Britain's DNA.
"We are world leaders in so many creative areas. From theatre to literature, video games, feature films, fashion, music and so much else, British artists lead the way and are celebrated around the globe.
"It's a success that has been created by the dedication, hard work and extraordinary creative abilities of our artists, it's not because of the EU."
He added: "Culture owes nothing to committees.
"Ancient Greece was the birthplace of our civilisation yet today, because of the EU's appalling policies, streets that were once filled with the world's greatest philosophers and playwrights are choked with desperate beggars and mountains of rotting rubbish.
"These are the realities of the EU. It's failing. The dream is dead. We need to move on."
Conservative Justice Secretary Michael Gove said he did not think people should be "swayed by celebrities".
Meanwhile Canadian PM Justin Trudeau has entered the debate, warning that Canada's own trade deal with the EU had taken more than ten years to negotiate and was yet to enter force.
"There's nothing easy or automatic about that," he said.
"Britain is always going to have clout, it's just obviously amplified by its strength as part of the EU. I believe we're always better when we work as closely as possible together and separatism, or division, doesn't seem to be a productive path for countries."
The former president of the European Central Bank, Jean-Claude Trichet, has defended Bank of England Governor Mark Carney's intervention in the debate last week, when he warned that a vote to leave could cause a recession.
Mr Trichet told BBC's This Week's World there was an "obligation" for the central bank to "say candidly what they see".
Those behind the campaign for the UK to leave the European Union said Mr Carney had breached his obligations on impartiality by emphasising only the risks of Brexit.
Leave campaigner Iain Duncan Smith told the BBC he "wouldn't expect" a major financial institution to back the Leave campaign "because they all wanted to protect the status quo".
And Lord Lamont, a former chancellor, has described "this daily avalanche of institutional propaganda" as "ludicrous and pitiful".
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