The story plays 100 years after(22XX) the Mega Man X storyline and follows the re-awakened Zero, who is fighting in a war between humans and Reploids, self-aware, human-like robots who are oppressed and hunted down by mankind due to a worldwide energy shortage crisis.

The series also introduces the Cyber-Elf system, which allows Zero to equip small helper beings known as "Cyber Elves" to assist him in combat.

[3] After feeding them with a certain amount of E-Crystals that are dropped by enemies, the elves can either provide permanent enhancements—such as increasing Zero's maximum health capacity, or grant temporary benefits—such as the ability to deflect bullets for a short time.

Acting like a rock-paper-scissors system, Zero gains three element chips (Fire, Ice, Thunder) that can be attached to all his weapons and changed freely.

[citation needed] Centuries after disappearing at the end of the Mega Man X series, Zero is found and awakened by Ciel, a 12-year old human scientist.

Zero, unsure of who he is due to temporary memory loss, protects Ciel and her band of Reploids from a group sent out to destroy them.

Knowing that Neo Arcadia will focus their attention on him, Zero decides to stay in the desert and fight endlessly in hopes of giving Ciel and the resistance the time needed to escape.

While Ciel tries to develop a new energy source to end the war, the new leader of the Resistance, Elpizo, instead prepares for a head-on invasion on Neo Arcadia.

While en route to Neo Arcadia to propose the Ciel System in hopes of making peace as there would no longer be a reason to continue the genocide on the Reploids, a large spaceship with the Dark Elf's energy reading crashes to Earth.

The Four Guardians, suspecting that Copy X is being heavily influenced by Weil, leave the Neo Arcadian army.

Wishing to capture it, Dr. Weil and Copy X authorise a missile to be launched at the district to incapacitate the Dark Elf.

However, Dr. Weil then succeeds Copy X as the new ruler of Neo Arcadia and announces his true intention for capturing the Dark Elf, which is to fuse the Dark Elf with Omega and link them with a colossal frequency transmitter that would enable Omega to control the minds of every Reploid on Earth.

The game starts with Zero, Ciel, and the Resistance members encountering a group of humans fleeing from Weil's forces.

Zero protects the humans, who then reveal to the Resistance that they are headed towards a large, nature-filled settlement in Area Zero, the location where the Eurasia colony crashed during the events of Mega Man X5 more than 100 years ago.

The large population of settlements like Area Zero attracts Weil's attention, who reveals a plan to use a meteor-sized space cannon called Ragnarok to vaporize all nature and make Neo Arcadia the only habitable location on Earth, which would force people to stay under his tyrannical rule.

[5] The English version of the Mega Man Zero series has also edited some instances of words such as "die" or "death," replacing them with terms such as "perish," "destroy," or "retire".

Review sources both criticized and praised the high difficulty level of the game and remarked that they were similar in nature to earlier installments in the Mega Man series.

[16] A manga series was authored by Hideto Kajima and serialised in CoroCoro Comic ran from June 2003 to February 2006.

This Zero is fitted with the "Hero of justice Circuits" allowing him to access his weapons like his over-utilized Z-Knuckle, and be ready for action but with a downside of him acting like a child.

In the end, Zero turns back to normal, Lito and Neige realized that Zero wasn't possessed but drank cola and got drunk.