Max is a genetically-enhanced human prototype hunted by her former military handlers through the edgy, underground street life of 21st Century America. Max is aided in her quest - both to avoid capture and reunite with her "siblings" scattered in the aftermath of their escape - by Logan Cale, an idealistic cyber-journalist battling repression and corruption in post-apocalypse.
After months of being imprisoned at Manticore, Max has resisted powerful attempts at re-programming and breeding and plans her escape from the genetics lab. She is aided in her breakout by the gentle but beast-like Joshua, an early Manticore creation, and together they release all the other Manticore creatures. Max attempts to reunite with Logan, only to discover that he is now number one on Manticore's most wanted list.
Manticore sends out a signal ordering all the escapees to return to a site where unbeknownst to them, awaits their death. While harboring a group of muddle Manticore escapees, Max is captured by a man who job it is to exterminate the remaining fugitives, leaving only Alec and the X6's to rescue her. Meanwhile, Lydecker contacts Logan when he gains information about Max that could be dangerous if it falls into the wrong hands.
Max and Logan look for Joshua, who is wandering Seattle looking for ""Father"", the man who created him. Meanwhile, Alec fights ordinary people in an underground club but when later caught by White, he must strike a bargain to kill three transgenics to save his life.
On Halloween night, Max finds her ""normal"" world turned upside down when the creatures she let out of Manticore are able to walk the streets freely without fear of exposure. As she and Joshua, with a crazy band of characters, race against time to find a headless body before it carries out its intended lethal mission, Max is faced with the reality that Asha and Logan are getting closer than ever.
Disturbed by Joshua's unusual behavior, as well as Alec's new job working at Jam Pony, Max's concern for Joshua is heightened when sector police killings are attributed to a ""beast-like"" creature. As Max races to try to figure out the mystery of the killings before more are committed, she makes a surprising discovery about who the culprit actually is.
Max discovers that Zack is not only alive but apparently benefiting from some cybernetic enhancements to his genetic engineering, however he does have memory problems. Knowing that Zack sacrificed his life for hers, Max puts herself at great risk, attempting to rescue him from his new ""owners,"" a vicious Seattle gang but when an attempt is made on Logan's life, Max is faced with a very painful decision.
Alec and Max set out to rescue an aquatic transgenic caught at sea from White, but the creature's mate throws a wrench into Max's plans. Meanwhile, Logan has a brush with death after he and Max get a little too close while babysitting his niece.
Max and Logan find themselves caught up in a spellbinding kidnapping case, that takes surprising turns when they learn the boy is the son of the infamous Mr. White. White, upon learning of Max's quest to find his son, decides to turn the tables and capture her instead and Max must race against time to save the boy, herself and discover the truth behind White's identity.
When Asha's militant group comes under fire, Max figures that it's all because of a Manticore-engineered military strategist, another transgenic called Brain. Brain sets out to protect Max as best he can, after he's called upon to discover who really betrayed the group.
While being haunted by music from the past, Alec must revisit one of his Manticore missions that went bad and resulted in the loss of his one true love. Max attempts to put the pieces of Alec's past together and upon discovery of the truth sets out to help him as best she can.
When Max and Logan finally find a cure for their genetically engineered virus, it turns out to be only temporary. Their time together is limited and to make matters worse they have to stop a strange Manticore creation that is on the loose in Seattle and preying on people.
Max must take on a cult of superhuman-blood addicts when she learns they're being led by a Manticore mutant intent on rebuilding an X-5 army. Meanwhile, Joshua falls in with the wrong crowd after Alec tricks him into delivering his packages for Jam Pony.
A genetically enhanced hypnotist targets Logan and Max, who reveals her true identity and Logan's secret activities before realizing that she is being manipulated as part of a deadly plan - but luckily she doesn't remember doing it. Meanwhile, the transgenic, Mia, also sets her sights on Alec, raising the stakes, leading him back into the boxing ring to make some money for some not-so-good fellas.
After a near-fatal incident with Logan, Max decides to end their relationship for good. A murder committed by Alec's Manticore twin, Ben, puts him under suspicion and places all of the transgenics in jeopardy...thanks to White and his leakage to the media. Meanwhile, Joshua finds the perfect woman, but can't find the courage to confess his secret.
Max must break her vow to avoid Logan after Joshua's friendship with the blind woman makes him a target of a transgenic manhunt in the sewers. Meanwhile, White leaks news of the human-looking X-5s to the media, leading to a wide-scale attack against the so-called ""monsters"" running amok and to the death of a someone dear to one of the transgenics.
Max's life is placed in more danger than ever before when she is hunted by the one person who knows her better than anyone -- her clone. Though even the existence of this exact replica is news to Max, she quickly realizes the imminent danger from an individual who can get inside her head and infiltrate her life like no one else. Dealing not only with this new threat but also the disintegration of her relationship with Logan and Joshua's disillusionment over not being able to go out in public, Max must race against time to figure out how to stop this deadly enemy before it's too late.
Max begins to develop strange markings on her body while leading a transgenic resistance against White, when he attempts to capture one of her ""brothers"". However, the transgenics are stunned by revealed secrets about their ""father"" that threaten all that they believe and stir up many more questions. Meanwhile, the Terminal City dwellers mount a campaign to battle the humans hunting them down, and Alec learns why Logan has been keeping his distance from his former friends.