Mackler was born in Manhattan, but when she was one her parents moved to Greenwich Village, later to Syracuse, New York, and finally to Brockport, New York, which is the setting for many of her novels. Mackler was always interested in writing, and from an early age tested her talent at it. Beginning at age four she created a newspaper with her best friend, recorded stories on a tape recorder, and dictated her stories to her mother who wrote them down for her. She lived in Brockport until leaving for college in 1991. From 1991-1995 she attended Vassar College where she obtained a degree in Art History in 1995. After college, Mackler drifted and lived in Seattle, Washington briefly before returning to New York City in December 1995. In 2003, Mackler married her husband and they now live in an apartment in Manhattan with their young son.

A few months after returning to New York City, Mackler took an internship at Ms. Magazine where she began writing articles and learning about the writing world. However, Mackler was never satisfied with writing for a magazine and in 1997 decided to take a course at NYU entitled Beginning Your Novel. During this time, Mackler began her first draft of Love and Other Four-Letter Words, it was published in 2000 by Random House Children's books. Her second novel The Earth, My Butt, and Other Big Round Things was released in 2003, the year Mackler and her husband married. This novel eventually won the Printz award, and the next year Mackler published Vegan Virgin Valentine. Her latest novel Guyaholic: A Story of Finding, Flirting, Forgetting...and the Boy Who Changes Everything was released in August 2007, and she is currently working on a fifth novel.

Carolyn Mackler was a self-proclaimed misfit in junior high; she never felt she completely fit in, and this has been a determining factor in her deciding to write young adult novels. Throughout junior high and high school, Mackler read many young adult novels in order to escape the belief that no one understood her. She read voraciously, but among her favorite authors were: Judy Blume, Lois Lowry, M.E. Kerr, and Norma Klein. Mackler writes on her website of the importance of novels for young adults and their influence on her:

"People often ask me now why I write novels for teenagers. Lots of reasons. One of the biggest reasons is that I honestly believe that, along with certain friendships, I was saved by the books I read during those years. They spoke to me in a way that nothing else did. They helped me feel less alone. They made me laugh. They made me feel like there was a world bigger than my high school."

Novels

• Love and Other Four-Letter Words (2000)
• The Earth, My Butt, and Other Big Round Things (2003, Michael L. Printz Honor)
• Vegan Virgin Valentine (2004)
• Guyaholic: A Story of Finding, Flirting, Forgetting...and the Boy Who Changes Everything (2007)
• Tangled (2009)