Five years after the events of Maniac Mansion, the mutant Purple Tentacle drinks toxic sludge from a river behind Dr. Fred's laboratory, which makes him far more intelligent and gives him a thirst for world domination. Answering a plea for help, the nerd Bernard Bernoulli travels to the Edison family motel with his housemates Laverne and Hoagie. When Purple Tentacle escapes to pursue his plans, Dr. Fred hatches a scheme to send the three friends back in time to stop the sludge at its source, but the faulty time machine strands each of them in a different era.