Born in La Jolla, California, McKellar and sister Crystal McKellar have maintained a friendly competition to see who gets more acting jobs. In fact, when the actress who would play Winnie had to be chosen, the last two actresses under consideration for the role were the McKellar sisters.

Danica and her family moved to Los Angeles when she was 8, and soon after, she and her sister began acting.

McKellar studied at UCLA, majoring in mathematics, and graduated summa cum laude in 1998. She coauthored a scientific paper which appeared in a peer-reviewed physics journal. Referring to the mathematical abilities of McKellar and her fellow student Brandy Winn, one of her math teachers, Professor Lincoln Chayes, was quoted in the New York Times as saying, "I thought that the two were really, really first rate". McKellar even provides free online math tutoring for her fans at her official internet website. At UCLA, she was a sister of the Alpha Delta Pi sorority. McKellar has an Erdős-Bacon number of 6.

Since then, she has had several guest roles in television series (including one with former co-star Fred Savage on Working), and has written and directed two short films. She briefly returned to regular television with a recurring role in the 2002-03 season of The West Wing.

She appeared in lingerie for a pictorial for the July 2005 edition of Stuff Magazine .

An Australian Hip-Hop act, The Winnie Coopers, named themselves after her well known character from The Wonder Years.

Danica McKellar has also lent her voice to the character Jubilee for the video game X-Men Legends.