At school, Ish is not picked for football during recess (something that happens to him on a regular basis). Later, while playing his football video game at home, he meets OT who tells him that he is just the person he is looking for and that everything Ish needs to know will be explained at the Chargers' home game on Sunday (which Ish and his mom "coincidentally" won tickets to). At the game, he follows the hot dog seller (Turns out to be the Chargers Rusher Bolt in disguise) and discovers a BlitzBot that is there to steal the Chargers' shard, but Ish defeats the BlitzBot with Bolt's help and gets back to his mom unnoticed.

Ish is led to a secret room beneath the Chargers' stadium, where he meets his "sub," a humanoid robot he will operate from a special control console to help the NFL teams protect the shards. Ish also gets a special pair of "guardian glasses" from Bolt. Later that night, he meets the Gameballz for the first time.

Ish receives a lock from the Gameballz that can teleport him from his locker at school to the locker room of any NFL stadium in the country. With it, he goes to New Orleans, where he attempts and fails to protect the Saints' shard from an army of corkscrew BlitzBots and a saw-armed BlitzBot.

Ish heads to The Big Apple, where he protects the Giants' Shard from the dreaded flying blitzbot disguised as a group of blimps.

Ish's Mom (who thinks Ish is on the school football team) starts to get suspicious of Ish running off to guard the Shards. Later, Ish defends the Broncos' Shard from a fast-and-fierce blitzbot and a heavy-duty blitzbot during a Broncos vs. Titans game, but the defeated heavy-duty blitzbot uses the last of its energy to hit Steed with a Corruption Football, turning him into a Blitzbot. Thus, he takes the Broncos' Shard, and when Ish gets home, he is caught by his mom coming out of his locker.

Ish doesn't tell his mom why he was in his locker, so she "grounds" him. Because of this, Ish is unable to protect the Colts' Shard from being stolen by a swarm of Free Football BlitzBotz.

Ish finds and destroys the fantasy football Blitzbot disguised as Calvin Johnson while protecting the Lions' shard, but after he goes back home, he accidentally leaves his locker open and one of his school bullies goes inside it.

With his lock stolen by the school bullies who are intent on finding out what is really going on, Ish must get help from the Rusherz to get from school to the NFL stadiums to defend the shards. To make matters worse, his Sub is damaged while defending the Seahawks' shard from a massive Air-And-Land Blitzbot attack and the shard is stolen, despite additional back-up from the Rusherz of the Falcons, Eagles, Ravens, and Cardinals.

Ish stands up to the school bullies and takes his lock back, but before he can use it to go to St. Louis, the bullies force their way into Ish's locker and end up going to St. Louis instead of Ish. The bullies find the Rams' shard, but one of them accidentally uses it to unleash a gigantic stadium Blitzbot.

The bullies flee from the stadium blitzbot and Rampage tries to hold it off, only to succumb to its barrage of corruption footballs and become a blitzbot. The Gameballz bring Ish to the battle and he attempts to stop the stadium blitzbot, but he fails and is forced to retreat with the bullies as the two blitzbots steal the Rams' shard. Worse, Sudden Death learns Ish's true identity. When Ish gets home, OT tells Ish to go to the pro football Hall of Fame for training.

Ish "wins" a trip to the pro football Hall of Fame and is chaperoned there by Marcus Allen. During his visit, O.T. reveals to Ish the secret of blitzbots living among humans and begins to teach Ish how to harness the power of the Rush Zone.

Ish continues his training at the pro football Hall of Fame by battling simulated blitzbots from different Super Bowl scenarios that are initiated by pulling out special rings from their display platforms and is supervised by Pack and Arrow Head, but when Ish pulls out the last ring, he finds a secret chamber with an amazing discovery within it; the Guardian's Playbook!

Ish returns from the pro football Hall of Fame, but starts to experience visions of Sudden Death defeating him. Thanks to the Guardian's Playbook, though, he is now extremely skilled at football (and the school bullies now properly respect Ish). Later, he visits the New England Patriots and Wes Welker shows him his new Sub, the Sub 2.0. Unbeknownst to any of them, Sudden Death has learned how Ish uses his locker to get from his school to the NFL stadiums and is now plotting something.

Sub 2.0. is put to the test when colossus blitzbots attempt to steal the Patriots' shard and it proves to be more powerful than the first. Later at school, a new kid named Ash makes a big impact at football during recess, and not only is Ash good at football, she's also a girl!

Ish realizes that he has a crush on Ash, but there may be more to her then meets the eye. Meanwhile, during rivalry week, tempers flare among the Rusherz in Pittsburgh.

A heavy-duty Blitzbot attacks a Dolphins game, and Ish is shocked to find Ash at the game, but the biggest shock is when it turns out that Ash is working for Sudden Death! Things get worse when Ash calls in another blitzbot to take Ish to the evil villain!

Ish is captured by Sudden Death and his mom, Shandra, discovers that Ish wasn't being honest to her about being on the school football team. John Madden and O.T. provide her with some answers as they escort her to safety. Meanwhile, Grizzly, Claw, Peg Leg and K-9 board Sudden Death's starship to save Ish, but after freeing him, they get cornered by some Blitzbots, Ash and Sudden Death himself. To make matters worse, Peg Leg has planted a football bomb in the ship and time is starting to run out!

Sudden Death orders his blitzbots to destroy Ish and the rushers while Ash remembers how OT thought she was the guardian but was wrong so she joined Sudden Death. Ish then puts on his guardian glasses and sees an escape pod through a wall. He tells the rushers to get him through the wall so Grizzly runs forward and the blitzbots shoot at him, blasting apart the wall in the process. Ish and the rushers then get in the escape pod and leave just as the football bomb goes off, destroying Sudden Death's ship, but when Ish looks back, he sees the head of the ship fly off. He returns to the charger's stadium to find his mom with all the rushers and some NFL players and coaches waiting for him. The stadium's televised screen then shows the head of Sudden Death's ship coming toward earth, and Ish tells them all that Sudden Death is coming and that they will stop him.

The Panthers, Raiders, Bills, and Jaguars' shards are all stolen and their rushers corrupted. Sudden Death then targets the last shard, the shard of the Dallas Cowboys, but Ash is having second thoughts about serving Sudden Death. Meanwhile Ish, his mom, and all the remaining Rushers listen as Michael Strahan gives a speech. They then see a huge dark shadow fall over the stadium.

During Super Bowl Sunday, Ish, the players, and the remaining Rusherz make a last stand to defend the Cowboys shard from Sudden Death. Positioning the head of his ship above the stadium, he sends in the first wave of blitzbots, which is easily defeated by Ish and the Rusherz. Angered, Sudden Death sends in a team of blitzbots that assemble into a super blitzbot. Ish and the Rusherz try to get away, but the super blitzbot crushes the Sub. Ish becomes uncertain of what to do next, but Shandra gets an idea...