Mr Manafort, who has come under increasing pressure for his ties to a pro-Russia party in Ukraine and his work as a lobbyist, handed in his resignation this morning.
Earlier in the week Mr Trump brought in two new people to head his team, effectively sidelining Mr Manafort.
"This morning Paul Manafort offered, and I accepted, his resignation from the campaign," said Mr Trump in a statement.
"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 is a true professional and I wish him the greatest success."
Hired at the end of March, he replaced Corey Lewandowski - an equally polemical figure - and was brought in to shore up Mr Trump's primary campaign team.