Stewie & Brian's Children were the result of Stewie's attempt to find a way for him and Brian to remain bonded after he feels that Brian isn't making as much time for him in "Stewie Is Enceinte".

After collecting DNA samples from Brian, Stewie creates a machine that impregnates him with their offspring. Brian reacts in shock at the news, and refuses to enjoy Stewie's pregnancy. But after his water breaks in McBurgertown, he is forced to help deliver the babies in his car when they can't make it to the hospital. After the birth, Stewie tries to keep the better looking ones separate, keeping Jack and Rose in a box together. Brian starts to bond with Finn since he looks the closest to Brian, although he originally believes his name is Dick.

Some of the children are born with birth defects and cause Brian and Stewie to worry about the cost of special schooling. After all but four die, including a deaf one that didn't hear Joe Swanson's lawnmower, Brian and Stewie discover that they separation was due to mixed signals on both sides, they agree to ditch Finn and the rest of the surviving kids at a shelter and return to their normal lives.