With people traveling between universes the Source Walls separating them are starting to break down. If they collapse another crisis would occur resulting in a single universe again.

Monarch is moving between universes assembling an army. His breaking of the multiverse would leave one universe for him to conquer.

Bob the Monitor is seeking Ray Palmer with anomalies Donna Troy, Jason Todd and Kyle Rayner. Jason faked his conversion to Monarch's side to give them a chance to escape from him and the Extremists.

Karate Kid has a virus that could result in the Great Disaster. He is seeking a cure in Bludhaven and has been joined in his quest by Firestorm.

Jimmy Olsen has gained unexplained powers and has joined Forage to find the killer of the New Gods.

The Monitors vote to go to war and take an active role in preserving the multiverse. They believe someone is manipulating all of these events. On Apokolips Darkseid has the participants in Countdown assembled like chess pieces on his table.

On Earth-15 a black-clad Superman is punishing a benevolent Lex Luthor for failing to make the human race better. This Superman sees humanity as a mistake.

NOTE:
With this issue, the series is renamed to "Countdown to Final Crisis."