4 Stewie Kills Lois (Part 1)

In the 100th episode, Lois and Peter go on a cruise, leaving Stewie and the family behind. Upset with Lois for leaving him at home, Stewie vows to carry out a diabolical plan. When Brian challenges him to actually do it, Stewie stows away on the ship, finds Lois and shoots her, seemingly killing her and resulting in Peter being blamed for her murder.