Alex Wilder, Gertrude Yorkes, Chase Stein, Karolina Dean, Molly Hayes and Nico Minoru meet at their families' annual gathering. When they see their parents performing the ritual sacrifice of a teenage girl, the shocked teenagers vow to turn the tables on their evil parents. Nico steals her mother's mystical Staff of One, Chase finds powerful gauntlets and x-ray goggles, Karolina learns she is an alien, Molly finds out she is a mutant and Gert inherits a genetically engineered dinosaur under her mental control. In order to get their children back, the Pride frames them for the murder of the innocent girl they had sacrificed. The runaways retreat to a hideout they call "the Hostel".
While stopping a robbery, the Runaways encounter a boy named Topher, who claims his parents forced him to aid them in the robbery. Deciding he is one of them, the group takes him back to the Hostel; the innocent Topher, however, reveals himself as an evil vampire and attempts to "turn" Nico by biting her, but Alex manages to rescue her and the two rekindle their relationship. Topher then goes after Karolina, but after a bite of her solar-infused blood, Topher explodes.
Former runaways Cloak and Dagger (informed that the teenagers had "kidnapped" Molly) arrive in Los Angeles to confront the runaways. While Cloak arrests the four older kids, Gert and Molly are finally given the chance to get into battle. Upon battling Cloak and Dagger and informing them of the real truth, the two superheroes promise to contact the Avengers to help the runaways take down the Pride; a mole in the Runaways, however, tips off the Pride. Catching up with the vigilantes, the Pride telepathically removes all memory of the meeting from Cloak and Daggers' heads, so they do not remember the Runaways.
The origin of the Pride is revealed, along with another revelation: the Hayes and the Deans plan on murdering the rest of the Pride in order to inherit a valuable gift by the Pride's benefactors, an ancient race of mythical giants called the Gibborim. The Runaways engage the Pride in battle and succeed in disrupting a spiritual ceremony, but in the end, Alex dies after outing himself as a traitor. When the Gibborim go on a rampage, the Runaways manage to leave alive, though the Pride themselves end up in the final explosion. Just when the Runaways escape, Captain America arrives to apprehend them. With their parents dead, Social Services separate the Runaways. Three exhaustive months after the destruction of the Pride, Karolina organizes a reunion, and the team heads off to an Avengers storage complex to retrieve Old Lace. The teenagers decide, rather than return to their new lives, to stay together and uphold a strong distrust towards adults. Although it was announced that Runaways would end with this issue, it was hinted that the series would come back again.
After a five-month hiatus, the Runaways fight the villains of Los Angeles attempting to fill the Pride's void. A future version of Gert travels back in time to warn the group that a boy named Victor Mancha will grow up to become "Victorious", the greatest villain of all time; before she dies, she warns them to kill Victor before he becomes too powerful. At the same time, a group of former teenage superheroes (called "Excelsior") are promised a $1,000,000 grant from a mysterious benefactor if they successfully detain the Runaways. The Runaways subdue Victor Mancha, and are later shocked to discover that Victor is a cyborg created by the killing machine, Ultron. With the help of Excelsior, the Runaways defeat Ultron, and Victor joins them, having no where else to go. After the battle with Ultron, Excelsior discovers its benefactor is Rick Jones. The story arc ends with a vivid shock: Chamber of Excelsior turns out to be a fraud, and is implied to be a resurrected Alex Wilder.
Karolina outs herself as a lesbian, and reveals she harbors romantic feelings for Nico, but Nico turns down Karolina's advances. As Karolina attempts to cope with the rejection, a Skrull named Xavin lands in Los Angeles and tells Karolina that he is her fiancée, due to an agreement between both their parents. Xavin informs Karolina of the fifteen-year long war between their races, and insists that their marriage is the only way to enforce peace. Although Karolina initially declines (on the basis that she is homosexual), Xavin shape-shifts into a female form. Karolina, finally agreeing, leaves her friends behind and departs with Xavin.
Escape to New York
Cloak, whose memories of the Runaways are restored, convinces the Runaways to travel with him to New York City and help solve a crime: someone posed as Cloak using MGH (mutant growth hormone) and brutally attacked as well as injured Dagger. When Chase and Nico end up in a dangerous situation with a drug dealer, Chase bluffs his way out by claiming their parents sent them there. A relieved Nico kisses Chase - who outright rejects her by saying Gert is his girlfriend, and the only thing keeping him "good". Gert and Victor run into Spider-Man who attempts to help them, but Nico knocks him out because Spider-Man is an adult and an Avenger. Meanwhile, after Wolverine scares Molly, she punches him through out of the church that Cloak had brought them to. In the end, the Runaways defeat Dagger's attacker (who was a fanboy of her's who believed she was his girlfriend), and they return home. Meanwhile, someone (implied to be a resurrected Alex) says that one of the Runaways is about to die.
During a super-human fight with "a dragon lady", young Molly Hayes is knocked unconscious, and washes down into a sewer system. After waking, she finds that she has been "recruited" by the Provost, who runs a crime ring that uses children to commit thefts. With many strategies, Molly leads her classmates into a defeat of the Provost. Although Molly invites them to join the team, all disagree - saying they would all go back to their families. After going home, Molly has a dream that shows her deepest desire: to go home with her parents.
As it turns out, it wasn't a resurrected Alex Wilder - it was a much younger version of Geoffrey Wilder, Alex's late father. After Victor has a nightmare about killing his friends under Ultron's influence, Chase confesses to being jealous of Victor, someone his parents would have loved. Nico tells Gert she wishes that Gert will become the leader, if something happens. The teenagers go to stop a crime in the middle of the night, but discover the younger Geoffrey Wilder and a new version of the Pride. In a twisted turn of events, the New Pride takes control of Victor, Gert finds out that Nico kissed Chase, and the New Pride kidnaps Molly. Before they can rescue Molly, they have to repair the Leapfrog - in this period, the Runaways' personal issues begin to get to them: Molly's absence, Gert breaks up with Chase, and Nico learns that the New Pride is getting their information through Victor (much to his shock). Just as the group breaks into a full-blown explosion, Karolina Dean returns to stop the fight.
After telling the team why she and Xavin have returned to Earth, Victor finds out that the new Pride has been using him as a spy cam, and finds that the broadcast was coming from the Minoru Summer Home. Xavin asks the team if he/she can help. The team then arrives at the Minoru Summer Home and finds that the new Pride has moved out and the weapons cabinet is empty. The Runaways find the New Pride at the Griffith Observatory and a fight starts, but instead of killing Molly, in the end, Geoffrey Wilder kills Gert. The New Pride, who'd been tricked by Wilder the entire time learn the truth about his intentions. Nico Minoru uses the Staff of One spell "Forget" to send Wilder back to his time, with his memory lost. In the present day, Chase runs away.
As the Runaways deal with the aftermath of Gert's death, an elderly shopkeeper manages to obtain a magic talisman belonging to Nico's parents . After claiming he just wants things to "go back to the way they used to be", transforms into a giant rampaging monster and attacks Los Angeles. Meanwhile, Chase "hires" Lotus (from "the New Pride") to help him resurrect Gert, by exchanging her soul to the Gibborim for Gert's - in the end, he pulls back. The Runaways learn of the shopkeeper's past; how he couldn't get over the death of his wife and was letting his pain out on the city. As the battle goes out of control, Xavin takes the appearance of the old man's dead wife, and Nico casts a spell to give Xavin her voice. Together, the two are able to calm the monster and return him to his human form. Chase reunites with the other Runaways at the Hostel and looks at Gert's portrait longingly, thinking of the deal he let go.
In the last arc featuring the creative team of Brian K. Vaughan and Adrian Alphona, Xavin expresses confusion about her/his identity to Karolina, and Chase learns from the Gibborim that the time during which he can resurrect Gert is short. Chase tells Nico that he intends to sacrifice himself on Gert's behalf, and shuts down Victor when he tries to intervene. He takes the Staff of One and leaves. Molly hears a voice that tells her to alert the others, and they follow Chase, using a urine trail that Old Lace leaves for them. Molly believes the voice to belong to Gert.
The team finds the end of the trail behind a doughnut shop and leaves Molly behind with Victor. A weak Karolina, a Staff-less Nico and Xavin enter the realm of the Gibborim, only to find that the giants will not accept Chase as a sacrifice. Apparently, his self-sacrifice was not considered "innocent", and instead the giants move to consume Nico. As all hope becomes lost, a conscious Victor and Molly enter the realm of the Gibborim to save Nico. Without their sacrifice, the Gibborim slowly fade to their deaths. As the team returns to the Hostel, they notice their security has been breached. Xavin realizes that she/he did not make the group invisible when they left; subsequently, Iron Man greets the children with a squad of S.H.I.E.L.D. Agents. In another reality, the Gibborim come face to face with the person who alerted Molly to Chase's plans in the first place: Alex Wilder.
Dead End Kids
After escaping Iron Man and S.H.I.E.L.D., Nico, Victor, Chase, Molly, Karolina and Xavin arrive in New York City. After a brief run-in with Wilson Fisk (the former "Kingpin" of crime in NYC) and the Punisher (where Molly socks him in the gut), the Runaways steal an artifact belonging to the late Gertrude Yorkes' parents. In a twisted turn of events, the Runaways escape to 1907 New York. Much to their shock, the Runaways are horrified to learn that the Yorkes themselves lived during this time, leading a super-powered group called the Sinners. The Runaways separate all over 1907 New York, looking for a new artifact to bring them to the present; it is at this point where Molly meets Klara Prast, an abused girl her age with an ability to control plants.
Nico becomes kidnapped by her great-grandmother, "the Witchbreaker", while Chase steals the Yorkes' time machine and disappears. Victor falls in love with a carefree girl named Lillie, and invites her to join them back in the present. However, the group stayed with ("the Street Arabs"), and is being targeted to death by the Sinners. This leads to a full-scale war in the streets of 1907 New York. Nico, who'd been trained by the Witchbreaker returns, more powerful then ever with a new Staff, along with Chase and his new Fistigon gloves. Right before the Runaways return to the present, Lillie tells Victor she can't leave her home, much to his angst. Klara Prast, however, does join them.
Nico, Victor, Chase, Molly, Karolina, Old Lace and Klara return to Los Angeles after finding a new hiding place at Chase's parent's former Malibu home. Chase gets a job at a radio station, and befriends radio shock-jock Val Rhymin, who murders the station manager in order to become in charge. Meanwhile, the remaining Majesdanians have arrived, with the desire to hunt Karolina down for the problems caused on their planet. Using a global spell ("Scatter"), Nico sends several of them over the world, but Victor later realizes that Nico's spell had unintended side-effects: it "scattered" the Runaways themselves. After fighting the Majesdanians, Xavin, shape-shifting into Karolina, leaves with them.
- Guest appearances: Wolverine, the X-Men, the Young X-Men
Val Rhymin and a magician named Mother work together to create a spell that will turn all of Los Angeles into zombies.The two of them decide to turn every plastic surgery patient in Los Angeles into zombies, because plastic surgery is one thing most of the citizens partake in. They infuse the spell with a CD, so any plastic surgery patient who listens to the CD will soon turn into a zombie. After testing it on Val's receptionist Lydia and finding out it works, Val plays the CD on the radio, which turns most of LA into plastic surgery drones. Val announces on the radio that he will cure the zombies if they loot the city and bring the valuables to the Hollywood Bowl by midnight.
After returning to the city from a camping trip to finding the city in chaos, Nico, attempting to reverse the spell (she finds out she can't) causes mass disruption by merging the zombies into one, large, monstrous entity. The team attempts to defeat the monster without seriously injuring any of the zombies, without much success. Eventually Nico casts a spell to cover the monster in oil. This breaks the zombies apart and leaves them incapacitated, however the street is left flooded with oil. Nico realizes that her magic has become much stronger since being tortured by her great-grandmother in the past. This explains why her scatter, knot, and oil spells have had unexpected side-effects.
The team travels to the KZIT radio station to stop the radio transmission, only to find that it is being broadcasted from somewhere else. However, they do find Lydia and save her from jumping out a broken window. Molly points out that Val will have to be at the Hollywood Bowl at midnight.
The team sneaks into the Bowl to find Val and Mother on the stage giving a speech. The police arrive and Val orders the zombies to attack the police. Niko stays to fight Mother while the others prevent the police and zombies from harming each other. Mother recognizes the Staff of One and realizes that Nico is a Minoru. He tells Nico that he "worked" with her parents many times and that the California Witchcraft Community thought she was dead. He then binds Nico with a snake and takes the Staff of One. The staff of One quickly changes into a large red dragon and eats Mother before reverting into a staff. Nico tells Karolina not to touch the staff ever again, although everyone has touched it in the past, because "things have changed".
The spell is reversed by playing the enchanted song backwards as advised by Molly.
Molly, after being invited several times psychically by Emma Frost, visits the X-Men headquarters. The Runaways have mixed feelings towards this visit, but all believe that it will end in a fight. Wolverine is assigned to give Molly a tour of the facility. They visit many areas of the headquarters, with Molly irritates the staff and is unimpressed with everything except the Danger Room, where she is built a unicorn and butterflies. Wolverine shuts down the construction and tells Molly to stop living in a fantasy land. Molly then begins to leave, finding that the X-Men are not the heroes that she imagined.
Nico, Victor, Chase, Karolina and Klara are interrupted in a cafe by a group of New X-men. They prepare to fight, but instead leave for a "no cover for mutants" dance club.
On her way out Scott tells her that he has sent a team to check in with the other Runaways. She leaves with Wolverine, believing that that the Young X-Men team and the Runaways will be fighting. On their way they are captured by a group of men in armoured suits. When Molly awakes she finds that she was kidnapped by an enemy of her parents. Years ago his team was trying to move onto Pride territory and he was paralyzed from the Haynes powers and forced to watch, while the rest of his team was killed. He had been paralyzed for the past seven years, unable to close his eyes or sleep and recently freed, now wanting revenge. Wolverine taunts the men into shooting him, asking Molly not to watch, however she does. The bullets break his restraints and he kills the men, but Molly stops him from killing the leader, saying super heroes don't kill. Wolverine tells Molly that her parents couldn't have been especially evil, since she turned out good.
Molly is returned to her friends. The others want to stay with the X-Men, but Molly refuses.