Leaving the European Union would be an "act of economic and political self-harm", David Cameron warned.
The Prime Minister said leaving the single market would be "needless and reckless" and insisted that Brexit would not help the beleaguered British steel industry.
Mr Cameron said cutting ties with Brussels would "hit our service industries hard" as he dismissed the idea of a Canadian-style trade deal with the EU as an alternative to remaining in the 28-member bloc.
Writing in the Daily Telegraph, the Prime Minister dismissed the suggestion - previously made by Leave campaigners including Boris Johnson - that the UK could strike a deal like Canada's.
And he also rejected claims made by Mr Johnson that leaving the EU would give "more freedom to rescue the British steel industry".
The Prime Minister said: "If we take the Canada free trade deal as a guide, we know it would be damaging for agriculture and manufacturing.
"Our beef and pork exports would face tariffs, and our car manufacturers forced to comply with rules imposing additional costs based on where they buy their components.
"And of course, there is British steel. We are doing everything we can to help British steel in these difficult times, but the idea that leaving Europe is the answer is a dangerous fallacy: more than half of our steel exports go to Europe."
His comments came as a poll indicated that Downing Street's tactics, labelled "Project Fear" by critics, were working, with the Remain camp on 51% and Leave trailing on 44%.
The Orb poll for the Telegraph found that only 5% said they are undecided, with those who currently say that they do not know how they will vote more likely to back the Remain campaign on June 23.
When certainty to vote is taken into account, the campaigns are virtually tied, with Remain on 49% and Leave on 48%.
Election guru Sir Lynton Crosby, who masterminded Mr Cameron's return to No 10, said ensuring their voters turn out will be crucial to either camp's chance of success.
Some 70% of Leave voters said they were certain to vote, while 61% of Remain backers will definitely cast their ballot.
Writing in the Telegraph, Sir Lynton said: "The fact that the Remain campaign are turning out a smaller proportion of the voters that support their cause, while current voting intention remains neck and neck, shows that the Remain campaign holds greater potential for success if it can effectively identify and motivate its supporters."
According to Sir Lynton, the poll suggests that Mr Cameron's Remain campaign has had "greater message discipline and focus" in the last month.
Some 39% now believe that the Remain campaign is "more credible and trustworthy", with Leave on 32%.