Chronologically, Metroid Prime takes place second in the fictional Metroid universe. Retro Studios wrote an extensive storyline for Metroid Prime,which was considered a major difference from previous Metroid games. Short cutscenes appear before important battles, and the Scan Visor can be used to read records from the Chozo and the Space Pirates. The Prime trilogy is set between Metroid and Metroid II, but sources such as Gradiente, Brazil's former distributor of Nintendo, and the Nintendo Power comics adaptation of Metroid Prime, set the games as occurring after Super Metroid. The Brazilian publicity even states that the Phazon meteor is a piece of Zebes, destroyed after Super Metroid. However, in Prime 3 it was confirmed that the meteor was a Leviathan from the planet Phaaze.
The game begins as Samus receives a distress signal from the Space Pirate Frigate Orpheon, whose crew has been slaughtered by the Pirates' own genetically modified experimental subjects. Upon arriving at the ship's core, she battles with the Parasite Queen, a giant version of the tiny enemies occasionally seen in the ship. Having been defeated, the Parasite Queen falls into the ship's reactor core, setting off the destruction of the ship. While Samus is escaping from the doomed frigate, an electrical surge destroys all of her Power Suit upgrades, and she encounters Ridley, now a cybernetic version of himself called Meta Ridley. She watches as her nemesis flies towards Tallon IV before giving chase in her gunship.
Samus initially lands on the Tallon Overworld, a rainforest-like area. She discovers the Chozo Ruins, the remains of the Chozo civilization on Tallon IV that was destroyed with the crash of a meteor, which contained a corrupting substance called Phazon and a creature known to the Chozo as "The Worm". Samus locates a Chozo temple in Tallon Overworld, and discovers that the temple houses a seal to the meteor's impact crater, which the Space Pirates are trying to break. The containment field is powered by twelve Chozo artifacts, which must be found to open the path to the crater.
Samus finds her way to the Magmoor Caverns, a series of magma filled underground tunnels. The Caverns are used by the Space Pirates as a source of geothermal power, and connect all of the game's other areas together. Following the tunnels, Samus journeys to the Phendrana Drifts, a cold, mountainous location home to an ancient Chozo ruin, Space Pirate research labs used to contain Metroids, and ice caves and valleys home to electrical and ice-based creatures. After obtaining the Gravity Suit in Phendrana, Samus explores the interior of the crashed Orpheon, and then infiltrates the Phazon Mines, the mining and research complex which is the center of the Space Pirates' Tallon IV operations. Here she battles Phazon-enhanced Space Pirates and obtains the Phazon Suit after she defeats the monstrous Phazon-mutated Omega Pirate.
During her exploration of Tallon IV, Samus finds the twelve keys to the Artifact Temple, and lores recorded by both the Chozo and the Space Pirates, providing some more insight about the history of the planet and the two races' colonization of it and other activities. As she puts the last of the keys in place, Meta Ridley appears and attacks her, but is defeated by Samus with some aid from the temple's defensive artillery. The Chozo Artifacts and Phazon Suit allow Samus to enter the Impact Crater, where she finds a Phazon-mutated beast called Metroid Prime, the source of the Phazon on Tallon IV. After she defeats it, all the Phazon on Tallon IV disappears and Metroid Prime sucks out the Phazon in Samus's Phazon suit in a last ditch effort to survive, reverting Samus's armor to the Gravity Suit. Samus then escapes the collapsing Impact Crater and leaves Tallon IV in her ship. In a post-credits scene only able to be seen if the player has collected 100 percent of the items, Metroid Prime uses the Phazon Suit to recreate its body, becoming the entity known as Dark Samus, the antagonist of Metroid Prime 2: Echoes and Metroid Prime 3: Corruption.