Identical twin brothers, Zack (Dylan Sprouse) and Cody Martin (Cole Sprouse), are new at their school and are struggling to make friends. The twins make friends with Max and Tapeworm, who are both unpopular. Zack and Cody soon meet Drew, a popular student at the school, who befriends the twins after learning that they live in the Tipton Hotel. After their new found popularity, they begin to ignore their real friends. Meanwhile, Mr. Marion Moseby (Phill Lewis), the hotel's uptight manager, hires Maddie Fitzpatrick (Ashley Tisdale), the candy-counter girl, to be London Tipton's (Brenda Song) tutor.

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A beauty pageant is held at the Tipton Hotel and Zack and Cody find interest in the contestants. Cody meets one of the contestants, Rebecca, and has a liking to her. Cody then enters the competition, hoping to get close to Rebecca. He then disguises as a girl named Tyreesha, who previously quit the competition. However, Cody then drops out of the competition because he wants Rebecca to win the pageant. So, Zack stuffs him in a closet backstage and takes his place. Cody is soon set free, then runs on stage to fight Zack, disqualifying them. Rebecca wins the competition.

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A hotel guest named Jason checks into the Tipton Hotel and Maddie seems to like him very much. When London invites her and Jason to see a concert, she asks Maddie to play along for one night and act rich. This backfires when Jason and his parents stay another night in Boston, and when Zack and Cody get involved. They get her into the imperial suite, but another guest, the Amputator, checks into Maddie's suite, so the boys must dismantle the suite in order for the wrestler to check out of the hotel.

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A hotel inspector takes control of the Tipton from Moseby, causing him to lose his job. But Zack and Cody cause chaos in the hotel to make the inspector look bad and get Moseby's job back.

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Zach and Cody have been spending way too much money which causes them to get grounded. But when they learn a celebrity couple are holding their wedding at the Tipton and that if someone can get a picture of the kiss they get $20,000.00, Zach and Cody will have to use their sly ways to sneak in and get the picture to pay off their moms bill. Will they succeed?

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Carrie receives anonymous flowers with a beautiful poem outside her door. She thinks they were sent by the concierge, but Zack and Cody don't think that he is telling their mother the truth. They set out to find their mother's real secret admirer.

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Zack and Max enter a dance competition, making Cody feel that Zack is better than him at everything. When Zack hurts his ankle by jumping on the bed, Cody has to step in for him, learning to appreciate his own abilities. London lends Maddie money for her parents, but then uses Maddie's indebtedness to exploit her ruthlessly.

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Maddie gets her prom to be at the Tipton after London convinces Mr. Moseby. Maddie also wants someone special to ask her to the dance. Zack, thinking that he is the one that Maddie wants to take her to the prom, shows up to the prom in a tux.

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Zack and Cody enter the Battle of the Bands that is held at the Tipton. Zack and Cody have some differences about their band, so they break up the band. Once it comes down to it, they realize that they work better together that apart.

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Cody goes to Math Camp with Tapeworm. Zack misses him and has London drive him there. London learns to drive.

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Estebon is accused of stealing from one of the guests at the Tipton, but Zack and Cody think that he is innocent. So, they set out to prove that he is innocent. London goes away on vacation, but cannot bring Ivana with her, so she had Maddie watch her. Maddie and Ivana bond, and Ivana is angry with London for leaving her.

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A accident with a football leads everyone to go crazy for a crazy crook's treasure.

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London's father loses his fortune, so he must sell all of London's expensive things. London must move into Maddie's house until her father can find a place for her to stay. London learns what it is like to be poor, and appreciates a life that she's never had to experience.

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London falls for the son of her father's enemy, who owns the St. Mark Hotel. They sneak around so they can be together and Maddie helps them. Zack takes advantage of Cody's ability to bake amazing cookies to make some money.

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After London starts and rumor about Maddie dating the lifeguard, Maddie unintentionally starts a rumor about London wearing real fox fur. Cody decides that he wants to be separated from Zack and experiments with his look, but it ends up getting him into trouble when the interviewer for a contest that he entered shows up.

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Mr. Moseby takes the twins to a baseball game so Carrie can get a day off, but he becomes the most hated man in Boston because he cost the Red Sox the game when he catches a ball for Cody. London sets Maddie on a date with one of her friends, but Maddie's hair will not cooperate.

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Jesse McCartney comes to stay at the Tipton. Zack, London, and Maddy all try to get a piece of him. Cody enters a science fair held at the Tipton.

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Facing the threat of summer school, Zack tries to fake dyslexia in order to get easier schoolwork.

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Everyone is convinced that there is a ghost in one of the suites. Zack won't stop playing pranks.

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When Zack and Cody's father arrives in town with his band, Zack decides that his dad is a lot more fun to be with than his mom, causing him to run away by stowing away on his dad's touring bus. Meanwhile, the boys' mom tries to make restitution for driving Zack away by forcing Cody to have non-stop fun with her.

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It's Christmas. Everybody gets snowed in the hotel while a pregnant Mexican woman and her husband stays there. As there is no way for the hotel to receive any oil, Arwin has to do what he can to keep everybody warm.

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Max impulsively kisses Zack after a basketball victory, causing them both to question their relationship, and the team to urge him to ask her out on a date. Maddie tries to curb London's compulsive shopping habits.

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Inspired by a motivational speaker who emphasizes to people to "Be the pilot of your own life", Cody sets out on a mission to get his friends and family to pilot their own lives, throwing everyone into turmoil and chaos. Meanwhile, Maddie and London compete--no holds barred--for a Trendy Teen title.

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Cody, then Zack become the objects of desire of a girl that neither boys are interested in.

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Mister Tipton gives the okay for the hotel employees to all get involved in the filming of a commercial promoting the Tipton Hotel.

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Zack and Cody show a young prince visiting from another country how to be an ordinary kid; Maddie and London pull an all-nighter waiting for visitors from outer space.

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