Big Pete and the school's stadium line painter, Mr. Beverly (whose squid (Edna), the school mascot, Pete has just killed), vie for the love of the math teacher (Ms. Fingerwood). However, Openface (pne of Big Pete's archenemies) tries to get the upper hand in his quest for the squid and in helping Mr. Beverly with his love for Ms. Fingerwood. He tries to get Ellen (the Petes' friend) to exploit that exact secret. Mr. Beverly was played by Richard Edson.
Big Pete and Ellen work on a science project to determine whether alien life exists on Earth, and make a new friend. Pete becomes obsessed with football hero Johnny Unitas and one life-changing play, while Ellen discovers that some things are best left unrevealed.
On a trip to the Hoover Dam, the boys' father is determined to defend his title of "King of the Road" from a challenging family, but lengthy bathroom breaks and lack of family cohesion threaten his success.
When Ellen is selected to dot the "i" in "Squid" in the regional high school marching band competition, Big Pete becomes jealous of her newfound closeness with her band partner, James Markle Jr. (nephew of their band director). Meanwhile, Little Pete tries to stop an interminable bus ride by reuniting lovelorn bus driver Stu Benedict with his ex-girlfriend, Sally Knorp.
Embarrassed to be working at his father's driving range, Big Pete hides his identity by dressing as the sort of bear that used to inhabit the area where the range is. Meanwhile, Little Pete helps Artie by perfecting his shot.
While Big Pete engages in a struggle against time to study for a test on the American Revolutionary War (with the fear that failing would cause him to wind up like the school's janitor, rumored to have failed the same test years before), Little Pete leads his gym class to try to beat his teacher's intramural dodgeball team.
On his way to school, Little Pete happens upon a garage band playing his favorite song: "Summerbaby" by Polaris. When he returns later that day, all traces of the band have vanished; Pete starts his own band to try to find them—and his song.
Little Pete destroys Dad's lawn in an experiment gone awry, and is forced to tunnel his way out of the house past a state-of-the-art security system in order to make it to the celebrations of his favorite holiday, the 4th of July. Pete meets Nona F. Mecklenberg (Michelle Trachtenberg), whose father is played by rock star Iggy Pop.
Big Pete's baseball team goes on a winning streak due to Little Pete's incredible knack for making distracting comments. The coach's win-or-die attitude, a super-cold slushy drink called the Orange Lazarus, and Little Pete's dirty tactics threaten to destroy baseball forever-- Big Pete is forced to make a choice between glory and the integrity of the sport he loves.
On the day that Daylight Savings Time ends in the fall Little Pete and Big Pete celebrate the extra hour by taking advantage of the "Time Warp" to do something momentous. This year, however, Big Pete is overcome by hormones and asks Ellen out on an official date. He enlists the help of Endless Mike Hellstrom, his enemy, to help the date go smoothly. Mike lends Pete his customized Ford Mustang convertible and teaches him the nuances of dating. When things don't work out right, Big Pete is forced to utilize the power of the Time Warp to fix things with Ellen before their friendship is lost forever.
Little Pete finds his guardian angel, Inspector 34, who inspects the Kreb Of The Loom underwear worn by the Wrigley's and their friends. Inspector 34 recruits Little Pete to be an Inspector while Little Pete shows him how to interact with normal people and have fun. Little Pete struggles with perfection while Inspector 34 lets his tendency of perfectness and his hormones go to his head. The newfound perfection of Inspector 34 begins to infect the neighborhood, and people begin behaving erratically. Little Pete must help everyone find a way to live in moderation between perfection and abnormality.
Little Pete decides to enter the annals of history by breaking the record for most houses visited on Halloween and tries to enlist the help of Big Pete. Big Pete is torn between his loyalty to his brother and the coming of age and abandonment of the childhood ritual of Trick-Or-Treating. He must decide whether to face the ridicule of his peers and go Trick-Or-Treating or to join the notorious "Pumpkin Eaters", a group of vandals who terrorize neighborhood "Halloweenies."
Ellen, fed up with math class, asks the question high school teachers dread most: "Why?" Her inquiry spreads like wildfire through the school and soon students are rebelling against the textbook knowledge forced upon them in every class. Ellen realizes that things have gone too far when math teacher Ms. Fingerwood disappears, and desperately tries to put things right.
The Wrigley family takes a fishing trip, and Big Pete contemplates mortality while Dad tries to catch a legendary fish named Bob. Also, after realizing the cruel fate that could happen to Bob, Big Pete tries to sabotage Dad's attempts on making the catch.
The end of Artie's influence over Wellsville comes in two parts. Supervillain and head of the International Adult Conspiracy John McFlemp (James Rebhorn) concocts a dastardly plan to rid the parents of Wellsville of the nuisance that is Artie forever, and threatens to destroy all that is unique about the kids of Wellsville. McFlemp extorts Dad and convinces him to get rid of Artie. The Petes, Ellen, and Little Pete's various friends start a campaign to find Artie, who disappears in Dad's car after a disheartening speech from Don (Dad). The campaign consists of a Bat-Signal-esque likeness of Artie's face, t-shirts, and various souvenir items. After Dad realizes his mistake and joins in the search, Artie is brought back to Wellsville, only to find Little Pete standing up to Papercut all on his own, demonstrating that Artie's protective influence is no longer needed.
Big Pete is stuck on a school bus departing for the deepest, darkest parts of the human psyche, as well as the creamed corn plant. During the bus ride, Pete befriends people he never thought he'd associate with, succumbs to the temptations of bullying, and is forced to cope with his actions and repent.
Little Pete decides to fake food poisoning in order to avoid another mind-numbing day at school during the stretch between winter and spring breaks. In an adventure that leads him from home to school and the various sites around Wellsville, Little Pete sees a classmate of his in a new light, gets a marshmallow likeness of president Eisenhower stuck in his nose, and gains a new perspective on the world that can only be appreciated on a sick day.
The Petes are entrusted with the key to the house while Mom and Dad go away on a trip for 2 days. Just when it looks like their plan to stage the ultimate bicycle race around the house is about to materialize, Big Pete is struck by hormones and instead chooses to vie for the attention of his latest crush. Little Pete sells the house in retaliation to the nicest family ever, the Krechmars. Big Pete tries to set things right with his brother and they attempt to regain ownership of the house before Mom and Dad return.
Little Pete's lucky penny runs out of luck one day, so he, Nona, Monica, and Wayne set out on a Journey to recharge it by letting the Midnight Express run over it. Pit Stain, Little Pete's arch nemesis, catches on and tails them, and Pete is forced to battle Pit Stain without the power of his lucky penny.
Big Pete tries to obtain the coveted position of Senior Life Guard while Little Pete fights to abolish the hated Adult Swim. Big Pete is forced to choose between the power of the life guard chair and his friendship with his brother.
Little Pete attends his first school dance and Big Pete is stricken by the lead singer of the hired band (Luscious Jackson). Pit Stain learns of Little Pete's fear of dancing and tries to exploit it, and Nona tries to avoid the embarrassment of dancing with her "Pop," (Iggy Pop) who takes the stage and sings a song for her.
Spring fever hits Wellsville hard and everyone begins dropping like flies. Big Pete is smitten by a star member of the tennis team, and Ellen realizes her true feelings for him. Little Pete falls for Eunice Puell, the mail lady, despite his most sincere efforts to avoid love through his mantra, "Love Bites." Nona is the last to go, finally falling for Little Pete. The results of this immense love triangle builds toward a climax.
Little Pete cooks up his biggest April Fool's prank ever, while Principal Schwinger (Adam West) enlists the help of Pit Stain, Hair Net, and Nightbrace to stop him. In the end, it's Schwinger and the Personal Hygiene singers that ends up getting pranked.
Big Pete tries to get a varsity letter and climb to the top of the social ladder the easy way by joining the wrestling team, and finds that individual sports are not a cakewalk. He trains for a confrontation at the big match with Endless Mike Hellstrom, and is coached by Ellen, a huge wrestling fan.
Little Pete prolongs Christmas for as long as possible after the holiday's end, in an attempt to keep the neighborhood in a constant aura of Yuletide Joy. His efforts are thwarted by a bitter garbageman who enjoys destroying Christmas trees.
Big Pete, Ellen, Wayne, Monica, and Stu Benedict make their way through a typical Saturday in Wellsville. Big Pete gets a haircut, Wayne tries out his new sneakers, Monica becomes a ninja, Ellen serves pizza, and Stu battles an endless traffic signal.