Various factions of Martians, led by John Carter and Gullivar Jones, ride into battle to protect their beloved Red Planet against nefarious mollusc-like encroachers. The molluscs launch themselves away from Mars, with their sights apparently set on Earth as their next conquest. When the first alien cylinder crashes in England, the League are called on to investigate.

The strange foreign cylinder turns out to be much more foreign than expected. The League barely make it out alive when the Martians turn their deadly heat ray on the hapless crowd of onlookers. The army is called in, and the League retire to a nearby inn to rest and prepare themselves. When yet another cylinder is sighted streaking towards Earth, Mr. Griffin decides to take steps that would be of mutual benefit to himself and the invaders...

The army's advance on the Martians' crater having been disastrously unsuccessful, the League are rushed back to the British Museum to confer with Mycroft Holmes. Quatermain, Nemo, and Hyde go on reconnaissance to the town of Maybury, where they encounter a terrifying Martian tripod. Meanwhile, back at the museum, Griffin brutally attacks Miss Murray and makes off with secret military defense plans. In light of Griffin's treachery, M decides to spread the League out: he sends Nemo and Hyde to defend London against the tripods, while Quatermain and Miss Murray go to see a certain doctor about his top secret government work.

Miss Murray and Quatermain arrive in the South Downs, where at the edge of an unnervingly large wood, they encounter a man named Prendrick babbling about animals and a doctor on some island. In London, Nemo manages to stay busy keeping the invaders south of the Thames and rescuing a small orphaned child. Hyde, however, is restless and impatient to get his claws into Martians, and around Griffin's throat. Griffin, for his part, advises his new cohorts that they'll need to do something about the Nautilus if they hope to advance past the river. Meanwhile, back at their room for the night, Miss Murray and Quatermain become intimately involved; at which point we finally see what it is Mina hides under her scarf. (It isn't pretty.)

While Nemo and his crew deal with a new Martian bio-weapon that has mired the Nautilus, Hyde heads back to the abandoned British Museum, where he corners Griffin. Meanwhile in the woods, Quatermain and Miss Murray reconcile after their misunderstanding of the previous night, until they are interrupted by the arrival of several freakish anthropomorphic animals. Murray and Quatermain meet with the creatures' master, a certain Doctor Moreau, and inform him of their mission. Back in London, Hyde has exacted his monstrous revenge on Griffin, and Nemo is none too pleased. And by then the Martian tripods have amassed on the south bank of the Thames and are ready to make their final assault.

Miss Murray and Quatermain see Moreau's "hybrid" safely back to London, where they rondevous with their co-workers at London Bridge.