As the "Heroes" continue to test their newfound extraordinary abilities, Claire tries to maintain a normal social life when a romance with the football quarterback takes a tragic turn. While Hiro convinces his friend that they are destined to travel to America to save the world, a frightened Niki follows instructions from a mysterious, unknown source that directs her to the middle of the desert. Meanwhile, Nathan uses Peter's accident to propel his political campaign. The elusive Sylar is being hunted by both Matt and the FBI, as well as Suresh, whose father's journal leads to potential clues.

A egotistical and super-charged Sylar goes to the Company to kill all the leaders, and inadvertently releases 12 super-powered criminals from the place's notorious Level 5 prison block during a fight with Elle. Peter, trapped in the body of one of the criminals, is set free as well and is forced to team up with a group for a crime spree. Meanwhile, Future Peter tries to fix his mistake with Nathan, as Angela takes over the company in the wake of Bob Bishop's murder and frees Noah Bennett to help the Company track down the 12 escapees and bring them back or eliminate them. In California, Claire learns more about her powers as she recovers from Sylar's attack. Hiro and Ando travel to Paris to track down speedster Daphne Milbrook who robbed them and learn that she is working for a darker power. In New York, Maya discovers that Mohinder's injection has changed him by making him super-strong, but also altered his personality. In Africa, Matt meats Usutu, an African shaman with a familiar power of painting the future. Elsewhere, Tracy learns that she has the power to super-freeze anyone and anything while dealing with a hounded tabloid reporter seeking any dirt on her and the shady Governor Maldon who are continuing to groom Peter for a position in the U.S. Congress.

Noah Bennett is stunned when Angela Petrelli assigns him a brainwashed Sylar as his new partner to track down the escapees from the notorious Level 5, as Peter, still trapped in the body of Jesse the Sonic Man, is forced to team up with a trio of deadly super villains who are on a murderous crime spree by holding up a local bank. Future Peter eventually releases Present Peter from his body-cell and shows him his dark future. In Africa, Matt learns more about his spiritual guide, Usutu, who also has the ability to paint the future. Meanwhile, Hiro and Ando track Speedster Daphne to Berlin to recover the mysterious formula, and find out that the rouge Haitian is behind it and working for another third party. In California, Claire asks her biological mother, Meredith Gordon, to teach her how to fight. Elsewhere, Micah Sanders, mourning the death of his mother is approached by the shadowy Tracy Strauss who asks him information about her past and why she and the late Niki Sanders are very identical looking, which leads to the mysterious Dr. Zimmerman, who may hold a clue.

Having time-traveled four years in the future, the future Peter shows his younger counterpart that people have access to drugs that give them various super powers and some of them will destroy the world. Past Peter is forced to run from the dark and evil future versions of Claire, Daphne, and Knox, all of whom work as killers for government agencies to track him down. Past Peter is forced to look for allies and finds one in a very subdued version of Sylar. From his spot in Africa, Matt Parkman has a vision of his future in four years in which he is married to Speedster Daphne and is still looking after Molly Walker whom also works for the agencies. In the present, Hiro and Ando are locked away in a Level 2 prison cell where their situation starts to drive a riff between them. Tracy learns more about her origins from Dr. Zimmerman, and Nathan receives more tips from the ghost of Mr. Linderman over his position for congress. Also, Mohinder learns that the powers he gave to himself are irreversible and could lead to disaster.

Fellow villains Knox and Daphne are sent by their emissary, Maury Parkman, on a quest to recruit Hiro and others to the Pinehearst fold. Adam Monroe is brought before the ringleader, who turns out to be the most powerful villain, who uses his power to heal. Matt Parkman arrives back in New York from his African adventure, and is confronted by Daphne with an offer to join their organization, but he instead wants a commitment from her. Hiro and Ando teleport to Africa to try to make contact with Usutu, the vision painter, for information on the persons behind all the recent events. Angela and the Company are paralyzed from recent events, and Noah Bennett is forced to team up with Sylar again to hunt down more escapees from Level 5. Peter goes to Pinehearst searching for answers, but is stunned to learn that his father, Arthur Petrelli, thought to be long dead, is the ringleader of the whole events, and who as the ability to physically absorb others powers by mere touch. Meanwhile, Claire and Sandra go on a mission to save Meredith from the clutches of Eric Doyle, a villain with abilities to control people mentally and physically. In New York, Nathan and Tracy try to trace their origins with Mohinder's help, but who has other plans for them.

Tracy and Nathan try to save themselves from a dangerous Mohinder who wants to use their synthetic power laced DNA to find a way to remove Mayas/his own powers. Mohinder turns to the dangerous, power-stealing Arthur Petrelli to help Maya, and in return, Mr. Petrelli asks for Mohinder's help in developing the secret formula to give people powers. Meanwhile, Sylar is given the task by the comatose Angela to save Peter from Arthur at Pinehearst, where he was captured and rendered powerless by his him. Also, Daphne is ordered by Mr. Petrelli to kill Matt, but finds the task difficult as she begins falling in love with him as he predicted. In Africa, Hiro is still searching for answers from the spiritual painter about who is behind Pinehearst and what their nefarious plans are for the world. In California, Elle approaches Claire and asks for her help to control her powers which leads to both of them forming an uneven alliance to venture to Pinehearst in New Jersey to find answers. Also, H.R.G. recruits Meredith as his new sidekick to track down more Level 5 escapees.

Under the guidance of Usutu, Hiro has a vision back in time one year ago to determine what forced Arthur Petrelli to fake his death and create Pinehearst. In the past, Hiro also watches the early days of the Company and how Mr. Petrelli and Mr. Linderman founded it, and their falling out with Angela who saw them as a threat to both Nathan and Peter. Also in the past, Meredith Gordon's origins are shown of how she was captured by Thompson to work for the Company, and of life of crime with her half-brother, whom is the blue-flame fire-starter Flint. Also, Sylar makes a discovery about his powers when he meets Elle for the first time and how she inspired him to kill in order to steal others powers.

Barely escaping from the evil and powerful Arthur Petrelli, Ando forces Hiro to teleport them back to Japan only to discover that Mr. Petrelli has erased most of Hiro's mind and who thinks he's 10-years-old, and still in school. Ando must try find a way to make Hiro remember his powers. Meanwhile, Sylar tries to reason with the captive Elle to force out her anger and to learn how to take her powers without killing her. Mr. Petrelli sends Knox and Flint out after Claire and Peter who try to find a way to outwit their pursuers. Matt Parkman tries to scan the comatose Angela Petrelli's mind to try to save her and learns that Daphne is a double-agent assigned to watch over him and that Mr. Petrelli has something against her. While Suresh continues to unsuccessfully search for the secret to the formula to give people powers, Nathan and Tracy pay a visit to Pinehurst where they meet with the manipulative Arthur Petrelli who offers Nathan the world in exchange for his loyalties and help. Nathan declines, but Tracy, eager to gain more power in politics, accepts.

Noah, Claire, Angela, and Meredith find themselves trapped at the Primatech by Sylar who locks them in the building and subjects them all to various mind games. Meanwhile, Matt, Daphne, and Ando seek refuge at the Mendez loft where Daphne plans to steal a sample of the power-giving formula to give to Ando who wants to rescue the powerless Hiro still trapped 16 years in the past, who continues to struggle to find his true origins with his younger self. Back in the present, Peter faces off against Nathan, Tracy and the security detail at Pinehurst to stop Mohinder from reproducing the formula, and finds allies in the form of Knox as well as Flint who also want to stop the production of the formula, leading to a fiery showdown for all.

Two months after the destruction of both the Primatech and Pinehurst, and the death of Arthur Petrelli, the now-villainous Nathan returns with a vengeance by persuading the U.S. President and the government to round up all people with abilities for containment and disposal, leading to Claire, Ando, Peter, as well as Tracy to become fugitives from the people who were their former allies. In Japan, a powerless Hiro tries to live through the super-charger Ando as his latest partner. In New York, Peter struggles to find a life for himself as a paramedic, but finds that his cannot hide from his past. Claire learns about Nathan's and Angela's plans for interment of people with abilities and sets out to warn Matt Parkman who learns more about his abilities from the spirit of the African spiritualist Usutu. Elsewhere, Syler travels to Baltimore to locate his long-lost father and ends up being the only one who escapes from a government dragnet led by a mysterious agent known only as 'the Hunter'. Mohinder also learns that he has been targeted, and that Noah Bennett is apparently working with Nathan as well.

Following the plane crash, the surviving heroes must team up with one another to try to survive the manhunt. Claire is quickly captured by Noah who takes charge of a "kill squad" to find the remaining people with abilities while Nathan deals with the overzealous 'hunter' Emile Danko whom becomes obsessed with tracking down all people with special abilities in his own lethal way. Mohinder and a powerless Hiro must rely on Matt Parkman's spiritual guide to help them. Daphne makes contact with Ando to help her find Matt, unaware of the people now targeting them. In New Jersey, Syler takes refuge in the house of an agent and tortures him to try to get information to what's going on and he forms an unlikely alliance with the agent's son Luke Campbell. Also, Peter teams up with Tracy to look for help, while she begins having second thoughts about running.