President Obama should "butt out" of the EU referendum, Nigel Farage has said.
The president is expected to use a visit to London next week to urge British voters to choose to remain in the EU at the referendum.
Republican Senator John McCain, who lost to Obama in the 2008 presidential election, has also warned Brexit would damage Western security.
Anti-EU campaigners and MPs are angry at the intervention in domestic British policy by the Americans.
Conservative backbencher Stewart Jackson told The Huffington Post UK that McCain should "mind his own business".
Speaking to LBC Radio on Friday, Farage said Obama was "the most anti-British president" there had ever been.
"We would be horrified if an American president got involved in a British general election campaign just as Americans would be horrified if a British prime minsiter was to say 'vote for Hillary'.
"So he should butt out."
The Ukip leader also attacked "lackeys in the White House" who said if Britain left the EU America would not sign a free trade deal with Britain.
"American presidents by precedent don't get involved or comment on general elections and nor should they with a referendum of this magnitude," he said.
Jackson, who like Farage is campaigning for Brexit, said: "I met Senator McCain in 2012 and greatly respect him.
"But he is wrong to interfere in the democratic process in the UK and assume that U.S. strategic interests are the same as the long term best interests of the UK electorate as they are not.
"I would respectively ask him to mind his own business and focus on US domestic policy not second guessing the EU referendum."
In a statement, Senator McCain said Britain’s membership of the European Union is “vital” for the security".
The chairman of the US Senate Armed Services Committee said: "Having a strong British voice in NATO and the EU helps ensure we make the most of the collective power of these institutions.
"The need for a strong and united Europe is greater than ever. The United States has long benefitted from British leadership in NATO and the EU – for instance, leading sanctions against Russia, providing vital support to Afghanistan and Ukraine, and grappling with the refugee crisis fueled by Vladimir Putin,” he said.
"The United States and the United Kingdom are confronting the most diverse and complex array of crises since the end of World War II. To meet these challenges, we need a comprehensive response that makes the best use of our collective economic, political, and military power."
He added: "British membership in the EU is a vital contributor to the security and prosperity of Europe and the United States."
Republican presidential candidate Ted Cruz told a campaign rally recently that Obama “will make it more likely that England will pull out of the EU” if he spoke out.
Earlier this week a cross-party group of MPs wrote to President Obama to urge him to stay silent. “This is a chance for the British people to choose the path of their country. Interfering in our debate over national sovereignty would be an unfortunate milestone at the end of your term as president,” the MPs wrote.
Boris Johnson has also accused the president of “outrageous and exorbitant hypocrisy” for advising the UK to remain inside the EU when the US would never accept a similar arrangement with other countries.
Downing Street has defended the right of foreign leaders to voice their opinion.
And Obama’s spokesman has said the president would "continue to make clear" that the United States wanted to see the UK remain inside the EU.
The president will visit the UK at the end of April. In a statement, the White House said Obama will “offer his gratitude to the British Government and people for their stalwart partnership with his administration and the American people throughout his presidency”.