Sabrina Spellman, en helt normal 16-årig, blir informert av tantene, Hilda og Zelda, at de er hekser. Hun bor sammen med dem i Massachusetts mens de forbereder seg på at hun skal motta sin hekselisens. Underveis kommer hun inn i mange problemer, mens hun prøver å finne ut hvordan de magiske formlene fungerer. Hun må holde det hemmelig for kjæresten hennes, Harvey, vennene Jenny og senere Valerie, og den overlegne erke fienden Libby, og hennes alltid mistenkelige viserektor, Mr. Kraft. Sabrina starter en karriere i journalistikk med sin første betalende jobb i Scorch, et alternativt musikkmagasin som fokuserer på alt og hva som helst "moderne".
Sabrina learns that she has been instructed to mentor a witch student, and it turns out that her student is the new girl at school, Dreama. However, Dreama's clumsy spells arouse Harvey's friend Brad's suspicions, revealing his true nature.
Sabrina turns green with envy, literally, after Harvey and Brad become best friends, triggering a case of Jealotosis - an intense green-eyed witch envy - when Harvey teams up with Brad instead of her to write an article for the school paper.
Sabrina zaps on a skin cream to appear more mature after college-guy Josh shoots down a romance because of her age, but the fast-acting lotion ends up being a rapid-aging potion.
Consumed with guilt over kissing Josh, Sabrina runs herself ragged trying to cook up a way to get Harvey to forgive her without having to say she's sorry.
Sabrina and Mrs. Quick uncover a scandal at school involving Mr. Kraft and misappropriated funds. Meanwhile, Sabrina finds Salem a date for his high school reunion, but it seems he is much more interested in her than she is in him.
When Sabrina is accepted to different colleges, she is pressured by Josh, Harvey and Zelda to choose their favorite, but her indecisiveness and need to please everyone causes her to be torn apart -- literally into four different Sabrinas.
