"Barry Bennett and I have resigned from the Carson campaign effective immediately," communications director Doug Watts said in a statement as he and campaign manager Bennett departed.
"We respect the candidate and we have enjoyed helping him go from far back in the field to top tier status," he said.
Carson's numbers in opinion polls have dropped ahead of the first contest - in the state Iowa on Feb. 1 - for the Republican nomination in the November 2016 election.
He now places fourth in many national opinion polls after enjoying an extended bid in the second slot behind front-runner, real estate mogul Donald Trump.
Craig Robinson, former political director for Iowa's Republican Party, said Carson's lack of visibility in such early-voting states as Iowa damaged him even though he had the chance to capitalize on his much-touted status as a political outsider.
"It only works if you're here. You need to have a constant presence. He vanished. He did these big family festivals in late July and then it was like he was done. He didn't come back until November," Robinson said.
In spite of the poll numbers, Carson's campaign on Wednesday announced a fourth-quarter fundraising haul of about $23 million, with 600,000 unique donors.
"We are proud of our efforts for Dr. Carson and we wish him and his campaign the best of luck," Watts said.