Zack and Cody try to make friends at school. When word gets out that they live at the Tipton, all of the cool kids hang out with them. In the end, the twins find out who there real friends really are. Meanwhile, Carey is practicing dance moves, while London teaches Maddie how to ask Lance out and Maddie tutors London in Math.
After getting bad grades on his report card, Zack decides that he needs a way to get good grades without having to study. When Bob, a boy with Dyslexia, shows up in his class, Zack decides that he can pretend to have dyslexia so he can have more time on both tests and reading. Meanwhile, London beats Maddie at chess, and soon Maddie becomes obsessed at beating London at chess.
Kurt, a rock-musician and the twins father, comes to the Tipton Hotel for a visit. Kurt will allow Zack and Cody do things that Carey would not approve of them doing. Zack decides to leave the Tipton when he gets in an argument with his mother about his homework, by stowing himself in his father's tour bus.
Prince Sanjei comes to the Tipton to be crown king, but when he tells Zack and Cody he wants to try being a regular kid, Cody poses as him, and Zack takes Sanjei to the mall. Meanwhile, London thinks she saw a UFO, so she invites Maddie over to stay up and look for one. Maddie though, is in it just for the free food and service.
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.
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.
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.
It's International Day at Zack and Cody's school and Zack decides to ask a guest named Kumiko, a Japanese opera singer, to be his project. After Zack loses Kumiko, Carey and the boys must fill in as Japanese singers for a convention being held at the Tipton. Meanwhile, Maddie and London get trapped in London's closet.
Zack and Cody go on a double date to a miniature golf course. Zack tries to impress his date, Ella, but things backfire on him. Cody and his date, Barbara Brownstein, have an intellectual attraction. London joins a bookclub with her rich friends much to Maddie's amazement. Carey tries to become a more healthy-living person.
When the Tipton holds Health and Fitness week, everyone begins to examine their eating habits. Cody helps Chef Paolo in an attempt to lower his cholesterol, while Carey begins to limit Zack’s sugar intake. Meanwhile, London and Maddie participate in a charity fashion show where they are both criticized about their looks, each taking drastic measures to change.
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.
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.
Maddie is back and is not getting along with Nia, while Estaban is not getting along with Patrick, and the rest of staff aren't getting along either. So, Mr. Moseby hires a professional to help the team get along. Meanwhile, when Zack causes some customers to leave, he and Cody schedule a bug convention at the Tipton to make it up to Mr. Moseby. However, due to his fear of bugs, he accidentally releases the bugs into the Tipton.
Tony Hawk checks into the Tipton; Maddie and London has a crush on their fencing instructor. While Zack and Cody are doing their science project, the problem is that Cody has a fear of germs, and when Zack makes a mistake when analyzing a germ from the kitchen and thinks it's a toxic type of black mold, the rumor spreads through the hotel and everyone starts panicking. Cody gets over his fear after he realizes that he can't go skateboarding with Tony Hawk wearing an anti-germs suit.
Zack and Cody befriend Travis, a kid whom they rope into helping them impress their dates. They then bail on Travis and go out with their dates, but lets Travis go with the girls instead. Maddie finds a stranger's phone whom she thinks is her crush (because she and the stranger have many of the same interests, which she found out on the lost phone). At the end, the owner of the phone was an old man, but Maddie takes an interest in the old man's grandson.
Zack tries out for the high school basketball team but realizes there's some stiff competition, the kind he didn't face in middle school, and worse yet, the giant, in-your-face Coach Little (Michael Clarke Duncan). Meanwhile, when they're rejected as cheerleaders, Cody and London form their own cheerleading squad with the help of Mr. Moseby.