The UK's standing on the world stage is enhanced rather than weakened by being a member of the European Union, Philip Hammond will insist.
The Foreign Secretary will tell business leaders that Britain's voice is "louder and more persuasive" as part of the 28-member bloc.
Although Britain "is and will remain a world-class player", it has a greater influence within the EU, he will assert in a speech in the City of London.
Addressing the Lord Mayor's Easter banquet, Mr Hammond will stress that he is a Eurosceptic but believes the UK is "safer, stronger and better off" as part of the EU.
By voting to remain in the EU on June 23, the UK will continue to play a leading role within the bloc pushing for trade deals and "countering Russian aggression" through sanctions, he will say.
"As an historic sceptic about the EU, I believe that, on balance, the benefits of the single market with the deal we have got and the unique terms of membership now offered to the UK, mean that we will be safer, stronger and better off if we remain in the EU," the Foreign Secretary will say.
The UK's "ability to project power and influence around the world is enhanced by our EU membership", he will tell the event.
"So to those who care passionately about Britain's influence in the world, I say that our voice will be louder and more persuasive if the United Kingdom votes to remain on June 23."
Mr Hammond's speech comes after Lord Owen, one of his predecessors as foreign secretary, warned that remaining in the EU would render the NHS "completely unrecognisable".
Lord Owen said he had "no doubt" that the health service would become more fragmented under agreements set in Brussels that the UK would be unable to ignore.
The peer, who campaigned as health minister to remain in the European Economic Community in the 1975 referendum, insisted the "momentum" in the EU meant the health service would be "ever more involved with EU competition, procurement law and marketisation".
Launching Vote Leave's Save our NHS campaign in London, he said: "That is the direction of travel. It is to make it completely unrecognisable."
Lord Owen argued that a Brexit would free the UK from the proposed Transatlantic Trade and Investment Partnership (TTIP) between the EU and US, which critics fear will lead to American health providers targeting the NHS.
The peer insisted severing ties with Brussels would allow the UK to take back control of the NHS and protect it from outside competition.
He said: "We are agreed in Vote Leave that whatever our political views on the present marketisation of the NHS, these decisions should for the future be for the UK Parliament and devolved administrations to take.
"It should not be for the European Commission nor the European Parliament."
He added: "It involves your families, it involves your homes, it involves your life. This is not a decision for a remote bureaucracy in Brussels."
The Government and European Commission have insisted the trade deal does not threaten the UK's health service.