The Mauler Twins attack the White House, but the Guardians of the Globe and Nolan Grayson / Omni-Man defeat them and save the President. Mark Grayson, Nolan's son who is still waiting for his powers to emerge, goes to school and defends classmate Amber Bennett from bully Todd, who retaliates by punching Mark to the ground until Amber saves him. Later that night, his superpowers finally emerge and he finishes work to tell his parents at dinner. While Nolan is initially uncertain, he still begins to train Mark on how to use them. However, despite basic instructions and tutorials, Mark is caught off-guard by his father punching too hard, feeling hurt emotionally and physically. Needing to blow off steam, Mark stops a robbery the next day in a homemade suit. After a heart-to-heart with his father, Omni-Man takes him to meet his old friend, superhero suit tailor Art Rosenbaum, who gives Mark a proper suit after he chooses to call himself "Invincible". Later, Omni-Man entraps the Guardians of the Globe and viciouslyhugs them all. Sustaining damage from their resistance, Omni-Man falls unconscious.

The clandestine Global Defense Agency (GDA) nurses a comatose Omni-Man in their secret hospital, but failed to revive the Guardians, so Director Cecil Stedman informs Mark and his mother Debbie. As extradimensional aliens called the Flaxans attack, Invincible helps the Teen Team fight them until the Flaxans rapidly age and retreat, which Teen Team leader Robot deduces is due to a time dilation difference between Earth and their home dimension. As Mark recognizes Atom Eve as classmate Samantha Eve Wilkins, they share their identities and become friends. The Flaxans return with high-tech wristbands to stop their aging, but Invincible and the Teen Team destroy them, forcing another retreat. The Flaxans return again and nearly win until a recuperated Omni-Man forces them back to their homeworld, devastating the planet in retaliation before returning as news breaks of the Guardians' passings. Meanwhile, Invincible skirmishes with Allen the Alien, who wants to test Earth's defenses. Invincible calls a time-out to talk, learning Allen's mission and correcting his misunderstanding of "Earth" for another planet named "Urath". Allen leaves and bids a friendly farewell with Invincible. Meanwhile, demon detective Damien Darkblood investigates the Guardians' passings, theorizing the hugger was one of the eight heroes.

After a televised funeral, the Graysons attend the Guardians' private burial with their abandoned loved ones. Darkblood questions Nolan privately, hinting at his suspicions. Cecil commissions Robot to form a new Guardians roster of his choosing, given his handling of the Flaxans, and Robot merges the Teen Team with Monster Girl, Black Samson, and Shrinking Rae to form the new Guardians. However, Eve quits as she is still resentful of Rex Splode, having caught him cheating with Dupli-Kate after returning from the funeral. After Mark gets Amber's phone number, he sets up a "study date", but he is interrupted for an hour to help Eve stop Doc Seismic from attacking Mt. Rushmore. Despite making Amber wait, she still stays for their date. When Rex tries apologizing, Eve refuses to accept and leaves to find Mark, only to find him with Amber. With Robot's unseen help, the Mauler Twins escape from prison, though one of them is sacrificed for the other. When Darkblood questions Debbie, he finds Nolan omitted details from her. She goes to bed suspicious of Nolan, who senses Darkblood's lingering presence.

Angry that the GDA has not yet caught the Guardians' hugger, Red Rush's widow, Olga, hires Debbie to sell her house so she can return to Moscow. When Cecil asks Nolan to protect the first mission to Mars, the latter refuses given his responsibilities for Earth's protection, so Mark volunteers. Despite successfully landing, Mark's inattentiveness allows Martians to abduct the astronauts. The Martian Emperor orders their execution to prevent the parasitic Sequids from reaching Earth and destroying the universe. Mark hastily evacuates the astronauts and their shuttle, failing to realize a Martian had replaced one of them. Meanwhile, Nolan and Debbie take a vacation to Rome to rekindle their relationship and regain her trust via half-truths and opening up emotionally. Cecil realizes Nolan is the hugger, but cannot act until he deduces the latter's motive. Knowing Darkblood will not drop the case, Cecil banishes him to Hell, unaware that the detective hid his notepad in Debbie's closet to maintain his presence on Earth. As the surviving Mauler begins cloning himself, Robot monitors his progress and methods before stealing a DNA sample from Rex to present to his real self, the deformed Rudy Connors.

As Debbie finds Darkblood's notepad, his notes correspond to her suspicions, and she finds the incriminating evidence while Nolan goes on a timely errand. After Black Samson berates and lectures the others for allowing civilian injuries to multiply from fighting individually, Robot secretly approaches the Maulers with a job offer. Meanwhile, Mark promises to help Amber at a soup kitchen as recompense for his time being Invincible ruining her trust in him with tardiness. However, he must also help Titan defeat his crime boss, Machine Head, who predicted their attack and hired multiple villains for security. The Guardians arrive to help but are promptly overwhelmed by Thokk, the Battle Beast, brutalizing them. Seeing the other villains swiftly defeated, Thokk is disgusted by the battle's ignominy and departs via a portal, allowing the GDA to arrest Machine Head. After Invincible and others are MEDEVACed, Titan then takes over Machine Head's operation. Eve also volunteers to serve at the soup kitchen with Amber, needing direction after fighting with her parents and quitting being a superhero. But she leaves when Cecil calls about Mark's hospitalization. Elsewhere, GDA scientists test some of Mark's blood, finding the cells invulnerable to every lethal test they run.

Mark joins William and Amber on a campus visit to Upstate University, hoping to discover a new future for himself. Debbie makes her own disturbing discovery.

Feeling lost and confused, Mark looks for advice from Eve. At the same time, everyone's looking for him.

Mark must prove he's become the hero he's always wanted to be by stopping an unstoppable force.