Twins Zack and Cody live on the top floor of Tipton, the hotel where their mother works as a singer. The perfect setting for this pair of two to do their thing.
Mr. Moseby and the Tipton Staff is challenged to a bowling competition, by its rival, Ilsa and her team. Zack is the star bowler for the Tipton, but ends up having to be replaced due to getting grounded. Zack's replacement must overcome his emotional scars, due to a past bowling incident.
The twins compete on a game show in which Cody does the mental challenges, while Zack has to do the physical challenges. Maddie mistakenly sends Mr. Moseby an angry e-mail which she tries to retrieve.
Zack has to take on the responsibility of taking care of Carey and Cody due to them being ill. Cody uses his illness to his advantage by making Zack his servant. Meanwhile, Mr. Moseby makes an announcement about the "Employee of the Month" and it's employees compete for that title.
When the twins find out about a ghost in Suite 613, Zack will stop at nothing to meet the ghost. With some help from Maddie and London, the twins come face to face with the ghost of Irene.
When the twins find out about hidden treasure in the Tipton, everyone goes into a frenzy looking for the money.
A girl at school likes Cody, but after he hires Zack to help, she falls for Zack instead. London's dog Ivana and Maddie's dog Scamp fall in love.
Maddie, Cody and Zack compete to get the best guest for London's online chat show. Luckily, The Cheetah Girls and Chris Brown are staying at the Tipton, but who will end up winning the competition?
Cody gets Zack a job at the school newspaper for the advice column since the previous person quits. When a girl he likes asks for advice, Zack tells her secretly to ask him out. So she does. But when she finds out about him giving the advice, Zack is in for a load of trouble. London can't sleep and Maddie, Mr. Moseby & Esteban try to help her sleep.
Cody searches for a summer job, and finds a "help wanted" sign at the local mini-mart. When the owner realizes Cody is friends with London, he will only hire Cody if he will set him up on a date with her. Zack discovers he is the smartest student in his summer-school class, all the other kids make fun of him.
Zack and Cody discover a machine of Arwin's creation that can transport people from one dimension to another. They hop in, and find themselves back at a mixed-up version of the Tipton Hotel; where London is a candy girl/babysitter, Maddie is an air-headed rich hotel heiress, and other personalities are switched.
It's the first day of high school for Zack and Cody. For the first time, London has to attend public school.
When Zack and Cody invite Arwin over for dinner he won't seem to leave. Carey is getting annoyed at him so she forces Zack and Cody to make him go. Meanwhile, Lance dumps London and she wants to find a way to get back with him.
Raven Baxter is stuck in Boston, where she has a vision that something bad will happen to Cody. After warning him, vaguely, he becomes paranoid. Meanwhile, Maddie tries to get London into wearing Raven's dress, but London is too stuck up to do so, until pop star Hannah Montana arrives at the Tipton, and wants to wear the dress herself.
Zack dreams that he has gone back in time to the Boston Tea Party with his family and friends, where an act of protest by Maddie inspires the him to launch a present-day battle to save a historical park in Boston that's being threatened to be demolished.
Carey needed some help, so Mr. Moseby ends up taking Zack and Cody to a baseball game. Mr. Moseby get into some trouble due to an incident at the game. London sets Maddie up on a blind date, in which Maddie ends up having a really bad hair day.
Zack convinces Cody, Jessica, and Janice to go see a scary movie, but when it's Zack who gets scared, Cody uses it to his advantage. Meanwhile, London likes a boy so she pretends to be poor for him to like her.
London's father goes broke due to an investment in a diamond mine. London now has to move in with Maddie. Zack and Cody wonder if their parents ever got them mixed up when they were babies.
Zack and Cody rent out London's Suite while she is out of town so that Stacie, a cute girl from school can have a sleepover birthday party at the hotel.
When a rich, cute guy stays at the Tipton, Zack and Cody help Maddie impress him by making him think she's rich. In the end, the guy finds out Maddie isn't rich but he still likes her.
Maddie is having her Sweet 16, and likes to have her party at the Tipton. On that same day, London decides to throw her own bash. Zack ends up trying to figure out what to get Maddie for her special day.
London (even though she can't sing or dance) gets the role of Sharpay in their school production of High School Musical instead of Maddie because Mr. Tipton is financing the director's play "Floss" on Broadway. Zack has to work backstage for detention and Cody gets the part of Troy.
Zack receives help for a history report from Mr. Moseby's grandmother, when she comes to visit. Meanwhile, Mr. Tipton forces London to get a job.
When a wheelchair basketball team visits the Tipton; Zack and Cody's basketball team plays an exhibition game against them. Meanwhile, Maddie is filming a movie for a student filming contest. She hires Lance, London and Mr. Moseby, but they're all terrible, so she has to figure out a way to make her movie a success.