Sometime after the events in Critters 2, Charlie MacFadden is tracking down the last of the Crites. A family of three - Annie (the main protagonist), Johnny (her little brother) and Clifford (the father) - stops at a rest stop when their car's tire pops. At the rest stop, Charlie warns them and Josh, the evil landlord's stepson, about the Crites. As this happens, a Crite lays eggs under the family's car and the family leaves, unknowingly taking the Crite eggs with them. Soon after they arrive at their tenement, the Crites hatch and kill the maintenance man Frank. When the landlord arrives, he too is eaten by the Crites after Josh locks him in Clifford's room, unknowingly trapping his stepfather with the Crites. Next, one of the residents is attacked and wounded on the leg by the Crites but manages to survive thanks to the help of Annie. Annie, her family and five others (including Josh) try to get to safety in one piece by getting to the roof of the building. Charlie arrives and destroys the remaining Crites, saving the remaining tenants.
The film ends in a cliffhanger with a containment pod sent from the Intergalactic Council crashing into the basement.