Several months have passed since the events of the mini-series. The Resistance's ranks have expanded and is using more secretive and militaristic methods to fight the Visitors, whose stranglehold on the Earth continues to grow.
Events soon take a turn for the worst for the Resistance, first when the Visitors' new battle armor and laser weaponry derails their military operations in saving captured humans on Visitor Motherships. Furthermore, the Fifth Column becomes hesitant to help when the Visitors become suspicious of treason in their ranks as well as the fact that they can't supply weapons since the Visitor's arms supplies are watched too closely. In the face of this situation, Resistance leaders Donovan and Parrish realise that without a special weapon or technological development, the war will end swiftly with the defeat of the human race.
Donovan formulates a plan to expose John, the leader of the Visitors on Earth, as a reptilian-based alien. The plan succeeds, helping the fledgling Resistance movement by encouraging extra members to join, and (more importantly) persuades CIA black-ops expert Ham Tyler - on behalf of a much more secretive and organised anti-Visitor conspiracy amongst the world's various Intelligence agencies - to work with the movement on increasing their effectiveness against Visitor targets, such as through the development and supply of armor piercing 'Teflon' ammunition. However, Julie is kidnapped shortly after exposing John, and subjected to the conversion chamber by Diana.
Meanwhile, the experiment that Diana began into cross-breeding using Visitor Brian and Resistance member Robin Maxwell has come to fruition and she gives birth to twins. The largely-human female, named Elizabeth, lives and suddenly begins aging at a rapid rate, exhibits great intelligence and odd abilities, while the largely-Visitor male dies. After examining its corpse, a mysterious biological organism is found to be toxic to Visitor physiology. Resistance scientists culture the organism into the "Red Dust", a bacterium which is deadly to Visitors but not harmful to life on Earth.
On a pre-approved day, the Resistance launches an attack on the ships while simultaneously releasing the dust into Earth's atmosphere, where the bacterium will endlessly multiply, making the entire planet deadly to Visitors. Meanwhile, Diana, who has since usurped command of the Visitor fleet, plans to use a mothership's doomsday device to destroy the Earth. Donovan, Parrish and many others journey to the ship and, after flooding it with Red Dust, killing every Visitor on board (excluding the Fifth Column thanks to an antidote in the form of a pill the Resistance made for their alien allies) they successfully disarm the device with help from Elizabeth (now looking around ten years old due to her rapid aging rate) and return to Earth victorious.