British Justice Secretary Michael Gove -- who backs a British exit from the European Union -- said earlier in the day that the agreement by Cameron and European leaders at a Brussels summit last week was not legally binding.
But Tusk, a former Polish prime minister, told the European Parliament that the deal was "irreversible" so long as British people voted to stay in the EU in a referendum on June 23.
"The decision concerning a new settlement is in conformity with the treaties and cannot be annulled by the ECJ (European Court of Justice)."
"But it will only enter into force if the British people vote to say."
Tusk said that however that a "leave" vote in the referendum meant the deal would no longer exist and that Britain would leave the bloc that it first joined in 1973.
"We will respect the decision of the British people. If the majority votes to leave this is what will happen," he said.
Tusk also urged the European Parliament to approve the deal so it can be turned into legislation, addressing fears that MEPs could choose to block key parts of the agreement.
Cameron says the deal will give Britain a "special status" in the bloc, allowing the government to limit welfare benefit payments to migrants and giving it safeguards as a non-member of the eurozone.
But the issue deeply divides Britain's ruling Conservative Party with the "Leave" campaign now supported by five cabinet members including Gove, as well as London's outspoken mayor Boris Johnson.
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