In 1982, a large alien spaceship stops above Johannesburg, South Africa. Reports suggest that the ship became stranded after a command module separated from the ship and dropped to Earth, nowhere to be found. An exploratory team discovers a group of one million unhealthy and leaderless members of an arthropod-like extraterrestrial species who are given asylum on Earth. Some of these aliens engage in criminal and destructive activities, which lead to demands from the human population for more control. As a result, the aliens - derogatorily referred to as "prawns" - are confined to a government camp inside Johannesburg, called District 9. The camp is secured and, even with a massive police presence, soon turns into a slum. In the first decade of the 21st century, Multinational United (MNU), a private military corporation, is placed in charge of policing and relocating the now 1.8 million aliens to District 10, a new camp 240 kilometres northwest of Johannesburg.
Wikus van de Merwe, a MNU field operative, leads the relocation with the serving of eviction notices on August 9, 2010. During the eviction Wikus confiscates alien weaponry and "aborts" their eggs with the use of flamethrowers. As this continues, some nearby aliens are shown distilling a mysterious liquid into a small canister. One of the aliens (designated "Christopher Johnson") resists. While raiding Christopher's shack, Wikus discovers and removes the container, accidentally spraying some of the liquid onto his face. That night Wikus falls ill and is taken to a hospital, where his left forearm is revealed to have mutated into an alien appendage. He is immediately taken into MNU custody. After discovering that Wikus can now operate alien weaponry due to his mutating DNA (the weapons being unresponsive to humans), they force him to test various energy weapons, including against a live alien target. The scientists then intend to vivisect him before he fully transforms, but a panicked Wikus overpowers his captors and escapes.
Now a fugitive, Wikus takes refuge in District 9 and returns to Christopher's shack. Noticing Wikus' arm, Christopher reveals that the canister contains a fluid that would allow him to reactivate the dormant mothership and take his people off the planet. After revealing the lost command module hidden under his shack, Christopher agrees to help reverse Wikus' genetic transformation if Wikus retrieves the canister from MNU. Wikus agrees and tries to buy weapons from the local Nigerian gang. Their leader, the paralyzed warlord Obesandjo, seizes Wikus, seeking to gain his ability to operate alien weapons. Wikus finds an alien firearm and kills some of Obesandjo's men before stealing a cache of weapons and escaping.
Wikus and Christopher break into the MNU offices and retrieve the canister fleeing back to District 9. Christopher, having just seen that MNU is performing medical experiments on his people, informs Wikus that he will seek help for his people before curing Wikus, which would take three years. Wikus knocks Christopher unconscious and powers up the command module. Soon after takeoff, one of the craft's engines is shot off by an MNU missile battery and it quickly crashes nearby.
MNU forces enter District 9 taking Wikus and Christopher prisoner, but Obesandjo's gang ambushes them. During an intense fire fight the Nigerian gang captures Wikus. From the downed command module, Christopher's son activates the mothership and an alien mechanized battle suit which frees Wikus. Wikus pilots the suit and rescues Christopher. Promising Wikus that he will return to reverse his transformation, Christopher activates a tractor beam in the mothership, which lifts the stricken command module towards it. Heavily wounded and in a much more advanced state of his mutation, Wikus crawls out of the wrecked battle suit.
The mothership begins to leave and Johannesburg's residents celebrate its departure. A series of interviews and news broadcasts are shown. The aliens are successfully moved to District 10, said to have a population of 2.5 million and growing. MNU's illegal experiments on aliens are exposed. Those interviewed theorize about Wikus' fate and hypothesize that Christopher Johnson might return for the refugees or declare war on humanity. Wikus' wife reveals that, having found a small metal flower on her doorstep, she has hope that her husband is still alive. In a scrapyard, an alien with a bandaged left arm crafts a flower out of metal.
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