Miss Cheerilee has been called out of Ponyville due to family matters, but the young fillies and colts still need a teacher. That's where you come in.
As a substitute teacher it is your job to take over for the teacher when they aren't there, and you have to follow the guidelines they left for you, but what happens when the class doesn't want to listen to those guidelines? From what Miss Cheerilee told you, the class can be rowdy at times, but is usually calm and controlled. You were also told to watch out for 3 fillies without their cutie marks. Why? You have no clue, but you're about to find out as the first day begins...
(Big Mac and Doctor Whooves will be introduced in a few chapters as adult friends of the main character :3)