Zuckerman first wrote for the sitcom The Fresh Prince of Bel-Air, and then went on to write and produce episodes for the Fox animated series King of the Hill.

In 1999, along with writer and producer Seth MacFarlane, he developed another Fox animated series, entitled Family Guy.

Zuckerman was partnered with Seth MacFarlane, the creator of Family Guy, and served as the series's original showrunner,[1] though has not a single writing credit.

Afterward, Zuckerman was brought in to develop the Fox animated series American Dad!, also created by MacFarlane.

In 2011, Zuckerman created the American adaptation of the Australian television series of the same name, entitled Wilfred, for the cable network FX, starring Elijah Wood and Jason Gann.