Paul Manafort has come under fire for his ties to Russian interests and former Ukrainian President Viktor Yanukovych.
He has denied any wrongdoing and it is not yet clear why he left.
Donald Trump’s campaign team was overhauled earlier this week with the addition of a new campaign chief executive and a new campaign manager.
The Republican presidential nominee, who arrived in Louisiana on August 19 to meet flood victims, has come under pressure in recent weeks after a series of controversial remarks and falling poll numbers.
Donald Trump said in a statement: “This morning Paul Manafort offered, and I accepted, his resignation from the campaign.
“I am very appreciative for his great work in helping to get us where we are today, and in particular his work guiding us through the delegate and convention process.”
Paul Manafort has faced public scrutiny in recent weeks after the New York Times reported that the Ukrainian government had uncovered ledgers pledging more than $12 million in undisclosed cash payments for his work with Viktor Yanukovych, who fled after an uprising in November 2013.
Ukraine’s Anti-Corruption Bureau is also investigating business deals worth millions of dollar that are linked to Paul Manafort.
Paul Manafort has vehemently dismissed the claims and denied any wrongdoing.
Hillary Clinton’s spokesman Robbie Mook said Paul Manafort was another example of Donald Trump’s ties to Russian President Vladimir Putin.
“You can get rid of Manafort, but that doesn’t end the odd bromance Trump has with Putin,” he said.
“Trump still has to answer serious questions hovering over his campaign given his propensity to parrot Putin’s talking points.”
Paul Manafort, a former adviser to George H.W. Bush and Bob Dole, only joined the Trump campaign in March, to help the billionaire secure the party’s nomination. He was promoted to campaign manager in June.
The announcement of new campaign chief, Kellyanne Conway, and campaign CEO, Stephen Bannon, earlier this week raised questions about whether it would diminish Paul Manafort’s role.
Paul Manafort was considered a guiding hand in steering Donald Trump toward a more conventional campaign as opposed to the anti-establishment brand of politics that made his primary campaign successful.
A hotel developer with no previous experience of politics, Donald Trump stunned the political world by beating far more experienced figures in the Republican Party.
Donald Trump faces Hillary Clinton, who has come under intense criticism over her email arrangements while secretary of state, in November’s election.
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