The Suite Life of Zack and Cody stars identical twin brothers Dylan and Cole Sprouse, as Zack and Cody, whose lives change when their mother Carey (Kim Rhodes), ends up landing a job at one of Boston’s finest hotels, the Tipton Hotel. As part of Carey’s contractual deal, the twins and her get to live in an upper floor suite of the hotel. Ashley Michelle Tisdale stars as Maddie Fitzpatrick, who plays the role of the hotel candy counter girl and part-time babysitter, that tends to having to put an end to Zack and Cody's antics. Brenda Song stars as the rich and spoiled hotel heiress, London Tipton; while Phill Lewis plays the role of Mr. Moseby, the Tipton Hotel Manager.
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.
A beauty pageant comes to the Tipton Hotel. Cody ends up becoming a contestant, because of a girl he likes to meet. Zack wants him to win, so they could use the prize money for new bikes.
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.
Zack and Cody have two pet rats as a science project. Mr. Moseby gives the twins tickets to a Red Sox's game to get them away from the hotel. Then a hotel inspector seizes control of the Tipton, because of Zack's mistake. London has a dog party for Ivana and Maddie has to plan.
When the twins get grounded for running around in the hotel, they try to take a picture of a $20,000 kiss so that they will no longer be considered burdens.
Carey gets a secret admirer. Zack and Cody end up hooking her up with the wrong guy. Now they have to find the right guy that is Carey's secret admirer. Mr. Moseby and London get ready for Mr. Tipton's arrival.
Zack and Max compete in a dance contest. Cody learns how to do magic. Zack injures himself, and Cody has to take his place in the dance finals. Maddie becomes London's servant after London lends her money.
Maddie has her prom at the Tipton Hotel after realizing there is nowhere else to have it. Zack thinks that he will be her date, but ends up getting dissapointed. Cody starts to act like a mime.
There is a Battle of the Bands competition being held at the Tipton Hotel. Zack and Cody, along with Max and Tapeworm compete against Maddie's band in which has London in the band.
Cody ends up going away to camp. Zack starts to miss him, and has to find a way to get to him. London ends up learning how to drive, with the aid of Mr. Moseby.
There are a couple of jewel thieves in the Tipton Hotel. Zack and Cody have to try and find out who it is to clear up someones name.
When the twins find out about hidden treasure in the Tipton, everyone goes into a frenzy looking for the money.
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.
London develops a crush with the son of a rival hotel owner, of which Ilsa is the the manager. Zack and Cody bake cookies to be served at a ball held at the Tipton.
London spreads a rumor she started about Maddie, and Maddie accidentally spreads one about London. Cody wants to look different, because people kept on thinking he was Zack. Cody has Zack fill in for him on an interview, because of a certain problem.
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.
Jesse McCartney checks into the Tipton Hotel and Maddie, London, and Zack break into Jesse's room. Zack collects discarded items belonging to Jesse, so he could sell them. Cody enters a science fair, and receives help from Arwin.
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.
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.
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.
Zack, Cody, and the entire gang get snowed in at the Tipton. Maddie rigs a ""secret santa"" bowl so that London will get her a gift.
Max ends up kissing Zack, after winning a basketball game. Maddie helps London with her shopping problem, because of something said by London's father. There is a surprise involving Carey and a certain someone.
Cody is inspired by a guest speaker and tries to do the same with his friends - to hilarious results. Meanwhile London and Maddie compete savagely in the fashion shootout of the year to get on the cover of Teen Trends.
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.
The Tipton shoots a commercial. The director happens to be a date of Carey's from 15 years ago whom she left in the middle of the date. He prevents Carey from trying out for the commercial—but in the end, Carey and the twins end up being in the commercial.
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.