Speaking at the European Business Summit in Brussels, the Polish official said, "I don't need to explain to anyone present here what dramatic consequences, also economic, would be brought about by Brexit."
Similar fears were voiced by British entrepreneur Sir Martin Sorrell who told the summit that he thought that the impact would not just be for the short term and that he anticipated "long term consequences for the British economy."
Addressing the opening of the two-day summit on Wednesday, Tusk said, "We have to maintain the internal European order."
He pointed to an "interesting" forecast by José Angel Gurria, Secretary General of the OECD, which was disseminated at the G7 summit.
Tusk said, "According to him, a UK exit would be a major negative shock to the UK economy, with economic fallout in the rest of the OECD, particularly in other European countries. By 2020, UK's GDP would be over three per cent smaller than otherwise. And by 2030, in a central scenario, GDP would be over five per cent lower."
Elsewhere, the leaders of BUSINESSEUROPE, the Brussels-based representative body, said they "firmly" wish to see the UK remain an "active and positive" member of the EU.
A statement issued at the summit reads, "The economic recovery continues to make in-roads across Europe and with significant challenges still ahead, now is not the time for division but rather for concerted action together to deliver peace, security and prosperity for all."
It goes on, "The UK has played a crucial role over the past forty years in shaping the development of Europe with trade and the single market at its core.
"Full access to the single market is a large part of the UK's attractiveness to foreign investors, yet several federations report that European businesses are postponing their investment decisions in the UK until the political situation becomes clearer."
The leaders said, "A vote to leave the EU will only heighten the uncertainty around current and future investments as some tough negotiations will then begin.
"A strong UK in the EU has been of mutual benefit to all of our economies in recent years, particularly through its contribution to greater trade and investment flows.”
He concludes, "The UK brings a strong vision and common sense approach to regulation to the EU table that is highly valued and is an influential voice we would not want to see leave.
"The referendum is a decision for the British people. But as representatives of businesses from 34 countries across Europe we very much hope the UK stays part of a reformed EU that is competitive, outward looking and delivers growth, jobs and prosperity for all."