O'Keefe was born in Cliffwood Beach, New Jersey and has Irish, Czech, Austrian, Polish and Swedish ancestry. When she was a child, the youngest of three sisters, she had a bowl haircut and was a self-described "dork." Her older sister was a model and she decided that she wanted to give it a try. She did, and says the modelling job brought her more confidence and more friends. She attended a Catholic school and grew from being the shortest in the class to the tallest (at 5'8"). Since leaving she has grown more and now stands at 5'10".

Midway through her junior year she left school to star on the soap opera Another World, playing Marguerite “Maggie” Cory. She then got a role on Nash Bridges, playing Cassidy, the daughter of Don Johnson’s title character. She and her mother moved to Hollywood, so Jodi completed her schooling by mail.

She made her big screen debut in 1998 in Halloween H20: 20 Years Later and later starred in such films as The Crow: Salvation, Whatever It Takes and Devil In The Flesh 2. She hit the spotlight when she portrayed her role as Taylor Vaughan in the teen flick, She's All That (1999). Jodi played Taylor Vaughan, the most popular (and conceited) girl in school and starred in it alongside Freddie Prinze Jr and Rachael Leigh Cook. When asked if it was hard to play such a character, Jodi replied, “Everybody knew a Taylor Vaughan in high school. Working in show business, you meet girls like that everyday.”

Jodi kept on filming both movies and Nash Bridges until the series ended in 2001. Later films have been Out For Blood where she played a vampire named Layla Simmons and Venice Underground. In 2005, she appeared for three episodes in the first season of Boston Legal.

Since then, Jodi has been at home and auditioning for roles.