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A U.S. government satellite crash lands near Piedmont, Utah, and two teenagers find it and bring it back to town. The town's inhabitants open it and release a deadly microorganism, which is later codenamed Andromeda by the United States Army. A team is sent from the Army's bio-defense department to retrieve the satellite, only to die from the disease themselves. The video footage recorded by the retrieval team and their strange deaths capture the attention of General George Mancheck, the head of the bio-defense department, who activates "Wildfire," a team of five scientists who are called upon when high-level bioterror threats occur in the United States. The team, headed by its creator Dr. Jeremy Stone, investigate Piedmont. They retrieve the satellite and rescue a hysterical 60-year old man and a colicky baby who have survived the Andromeda outbreak.

In an isolated underground laboratory, the Wildfire team begins their examination of the downed satellite and the two survivors. The laboratory is powered by a small water-cooled nuclear reactor. In the event of a contamination breach, a 15-minute self-destruct sequence would be automatically initiated; however if the activated sequence is deemed unnecessary, Major Bill Keane, designated by the Odd-Man Hypothesis, is the only person able to deactivate the sequence, using his pass key and right thumbprint.

The scientists begin their analysis of the Andromeda strain by recovering a sample from inside the satellite. They initially discover that the microorganism is contained within a delivery system of buckyballs, a technology more advanced than anything known at present. The team theorizes that Andromeda may have an extraterrestrial origin, as it has no DNA or amino acids. The team discovers Andromeda is an airborne microorganism that kills its host by entering the bloodstream through the lungs and coagulating the blood in the body, causing death within 10 seconds via a blood clot in the brain. Those who manage to survive the blood clot become extremely violent and suicidal. It is revealed that the two survivors from Piedmont had not been affected by Andromeda because of their acidotic blood. However, all initial tests with antibiotics and chemical agents regularly used to kill other microorganisms show no effect on Andromeda.

Cable news reporter Jack Nash becomes aware of some of the events related to the fallen satellite and Andromeda. As he investigates further, Chuck Beeter, the Director of the NSA, uses General Mancheck's aide, Colonel Ferrus, to perform assassinations to prevent knowledge of Andromeda from reaching the civilian population. Nash travels to one of the temporary Army outposts performing quarantine procedures, and witnesses the effects of Andromeda spreading through various modes of transportation. He becomes a target of assassination due to his presence at the outpost, but manages to escape Ferrus and his subordinates.

In an attempt to neutralize the problem, the President of the United States authorizes a small tactical nuclear strike on the quarantine area in hopes of completely irradiating and destroying Andromeda. When the Wildfire team is informed, they realize that they have not reviewed the test results for irradiating Andromeda. They find that the microorganism grows at an exponential rate when irradiated. The Wildfire team alerts the President, and the air-strike is called off before the pilot launches the nuclear missile. However, as the jet continues to fly over the quarantine area, the pilot reports a malfunction of the aircraft's controls. Through video feed, the Wildfire team and President watch in shock and horror as all plastic components of the aircraft, including the pilot's visor, disintegrate. The nuclear missile is re-armed, the jet and missile crash into the ground, and the missile detonates, irradiating the quarantine area. The team examine the footage of the crash, and realize that Andromeda did not attack the pilot until after the missile launch sequence was halted, leading the team to believe that Andromeda has the ability to think. They also realize that Andromeda has mutated into several variations, with different means of spreading and different effects.

As Andromeda grows and mutates into more virulent forms, the Wildfire team continue their tests to find a way to stop Andromeda before it reaches Las Vegas, the closest city to the quarantine zone with an international airport. Further studies reveals Andromeda is actually a sulfur-based compound. A set of tests with phages reveals that one phage has the ability to kill Andromeda. However, repeated tests with this phage prove unsuccessful, causing the Wildfire team to theorize that Andromeda can communicate through an unknown mechanism between its separate parts. A binary code encoded on buckyball casings with potassium and rubidium atoms is also discovered. The information included the 6-digit number “739528” and the word “Bacillus infernus” encoded in ASCII, and a bitmap image of a symbol with interlocking triangles. Bacillus infernus is the name of an archaebacterium found only at the thermal vents on the ocean floors. At this time President Scott was championing the new and controversial industry of thermal vent mining, and it was likely that the mining would eradicate the bacteria. The encoded information causes Stone to realize Andromeda must have a connection with Earth, and leads Stone to force General Mancheck to reveal the truth about the satellite.

Mancheck reveals “Project Scoop,” a confidential mission to examine a wormhole that had appeared near Earth. It consisted of a satellite sent to collect organic samples, but it malfunctioned during the mission and crashed. With this information, the Wildfire team infer that Andromeda could have been sent from Earth's future, possibly because society in the future could not destroy the contagion due to a lack of a natural resource - Bacillus infernus.

Tests with Bacillus infernus reveals that the bacterium easily consumes and destroys Andromeda because of Andromeda's sulfur structure. The Wildfire team begins to grow large amounts of the bacterium in culture vats, intending to release the cultures over the quarantined area once a sufficient quantity is grown. The team also begins to destroy the remaining samples of Andromeda in the lab in an attempt to prevent Andromeda from communicating the nature of the tests with its other parts. Eventually, enough bacteria are grown and they are sprayed over the quarantined area, eradicating all traces of Andromeda from the environment.

As part of a government conspiracy to preserve Andromeda for future use, Colonel Ferrus blackmails Dr. Barton to keep a sample. The sample mutates and disintegrates the sample casing, setting off the lab's contamination breach sensor and initiating the self-destruct sequence. The self-destruct sequence also causes the flashing emergency lights to turn on, triggering Chou's photosensitive epilepsy, which causes him to inadvertently destroy the self-destruct control panel on the lab level of the complex.

With the elevators deactivated due to the self-destruct sequence, Keane decides to climb to the control panel on the level above through the lab's main exhaust vent. However, the pipes and other components in the vent have begun to deteriorate due to the mutation in the Andromeda sample. The pipe Keane climbs suddenly bends, dangling Keane above the radioactive water at the base of the vent. Before falling, Keane manages to throw his badge to Stone. Realizing Keane's right thumb is also required to shutdown the self-destruct sequence, Chou sacrifices his life to enter the radioactive water to cut off Keane's thumb for Stone. With Keane's thumb and badge, Stone reaches the control panel and deactivates the sequences.

As the remaining Wildfire team attends the funerals of their fallen colleagues, both General Mancheck and Colonel Ferrus are secretly assassinated. Dr. Stone reveals some of the events to the public in an interview with Jack Nash. In the final scene, the saved sample of the Andromeda is inserted into a containment compartment with the access code “739528”, held in a vessel marked with a symbol with interlocking triangles. Director Beeter watches over the operation on the computer in his office. The camera then zooms out, revealing Andromeda has been stored within a space station orbiting Earth.