Milo Murphy is the personification of Murphy’s Law where anything that can go wrong will go wrong. Suffering from Extreme Hereditary Murphy’s Law condition (EHML), Milo always looks to make the best of the cards he’s been dealt and his endless optimism and enthusiasm can turn any catastrophe into a wild adventure. Together, he and his friends will learn that it’s all about a positive attitude and not to sweat the big stuff… and it’s all big stuff.
Milo and his friends meet up with Phineas, Ferb, and their Danville friends to try to stop Derek and his Pistachions from taking over the world.
Scott the Undergrounder gets a date with Milo’s science teacher, Miss Murawski.
Zack Underwood, a new kid in town, meets Milo Murphy, the unluckiest kid in town. Because of Milo's misfortune, he and Zack both miss the bus for school, so Milo shows Zack a "shortcut" to school, while attempting to avoid wolves, bees, fire, and even an alien abduction. Meanwhile, Melissa Chase, a friend of Milo's, collects lunches as wagers from other students on whether or not Milo and Zack will make it to school before the bell rings.
Milo, Zack, and Melissa's subway car gets derailed on their way to a field trip to the museum. While trying to find their way to the museum, they encounter a society of construction workers who have been underground for a long time.
Milo attends his high school's football game, which turns into an extraordinary, explosive sporting event.
Milo, Melissa, and Zack try to protect an egg for a science experiment.
Sara wants to see The Doctor Zone Files movie with Milo, but worries about potential problems.
Milo and Zack try to help Melissa overcome her secret fear of roller coasters.
Milo and Melissa share their most embarrassing stories, but Zack refuses.
The gang participates in a school event that combines the Academic Decathlon and the Athletic Decathlon.
Milo's science class deals with a bored substitute. Meanwhile, Cavendish and Dakota hide in the classroom's closet to hide a substance that will help pistachios grow.
Milo and Zack go fishing with their dads. Meanwhile, when their phone battery dies, Cavendish and Dakota interfere with Brick and Savannah's time travel mission.
At a donation drive, Milo accidentally gives away his mother's precious vintage T-shirts. Cavendish and Dakota are assigned to protect the pistachios at the zoo.
Amanda does everything she can to make sure the school dance goes off without a hitch. Cavendish and Dakota go to the dance to attempt to prove without a doubt that Milo is another agent attempting to thwart their plans. Mort mistakes Cavendish and Dakota for vampire hunters.
Milo, Melissa, Zack, and Mort's band enters the battle of the bands. Zack discovers his old boy band is competing in the battle.