"Family Guy" creator, writer, voice-over actor and director MacFarlane will be the first emcee in the network's history to preside over consecutive Comedy Central roasts. He previously served as host of the roast of David Hasselhoff.
The show featuring celebrities poking fun at Trump is to be taped March 9 and will air later in the month.
Roasters and attending talent will be announced shortly, Comedy Central said.
Trump is a real-estate mogul and the star/producer of TV's "The Apprentice" and "The Celebrity Apprentice."