He studied animation at the Rhode Island School of Design and then animated Dexter's Laboratory and Johnny Bravo for Hanna-Barbera.
His work on Family Guy earned him many honors and recognitions, including Primetime Emmy Awards, a Webby Award, and a Teen Choice Award. He hosted the 2013 Oscars.
He is the son of Ann Perry and Ronald Milton MacFarlane and grew up with a younger sister named Rachel MacFarlane.
He hired several popular actors to voice Family Guy characters, including Seth Green.