Macdonald, currently Channel 4's social affairs correspondent, will take up the newly created role of health and social care correspondent.
The former Sunday Telegraph journalist, who has been at Channel 4 since 1999, will focus on issues surrounding the delivery of health care and its impact on patients, including treatments, drugs and ethical issues.
After ten years on Channel 4 News as a reporter, Keme Nzerem will become sports reporter as part of the broadcaster's renewed focus on sports news.
His new role will combine match and events highlights coverage with sports journalism and investigative projects. A key area for Nzerem will be disabled sports as Channel 4 is the main broadcaster for next year's Paralympic Games.
"The reforms and upheavals in health and social care affect everyone in one way or another," said Macdonald.
"From the plans for the NHS to the massive changes in the welfare system, to the problems thrown up by the ageing population, it will be my job to report and analyse what is going on and explain how it will impact on all of us."
Nzerem added: "Our sports coverage should reflect the way our viewers feel about sport, and that means ranging from unparalleled excitement to well informed scepticism.
"Our coverage will champion the values we bring to every story - dogged determination to get to the truth, with a spot of mischief. It's going to be great to put a Channel 4 News stamp on this area of the news agenda."
The changes are part of a revamped presentation lineup at Channel 4, including political correspondent Cathy Newman becoming the third main presenter alongside Jon Snow and Krishnan Guru-Murthy.
Channel 4 has also hired the BBC's Matt Frei as its new Washington correspondent and appointed Newsnight's Jackie Long to the newly created role of social affairs editor.
Discussing the new roles for Nzerem and Macdonald, Channel 4 News deputy editor Martin Fewell said: "Creating these new roles is a signal of our intent to expand our coverage in these areas.
"We know that the issues in health and social care are top of the list when it comes to viewer concerns - and on more than one occasion this year, sport news has headlined our programme, whether that be through FIFA, Olympic tickets or cricket match fixing. Expect to see even more from us in these areas now we have the best people on the case."