Born and raised in Wilmington, Delaware, Shue replaced Claudia Wells as Jennifer for Parts II and III of the trilogy. The scene from the very end of Back to the Future was re-filmed for Back to the Future Part II, with Shue performing the lines that Claudia Wells originally delivered. However there are several noticeable differences between the two versions. In addition to being 17-year-old Jennifer for most of the film, she spent hours in makeup to appear for a few seconds on-screen as 47-year-old Jennifer.
Shue's first major film role was as the girlfriend of a California teenager (Ralph Macchio) whose best friend was a wise old man (Pat Morita), in the 1984 hit The Karate Kid. She received top billing as the star of the 1987 comedy Adventures in Babysitting (second billing went to her co-star, Maia Brewton, who had been Sally Baines in Back to the Future). In 1988, she was Tom Cruise's girlfriend in the film Cocktail, before being cast as Jennifer for the two sequels to Back to the Future.
In 2012, she joined CSI: Crime Scene Investigation as a regular, playing Julie "Finn" Finlay.
She also voiced Detective Lacey Sole on the American Dad! episode "Less Money, Mo' Problems" in a mock drama titled Shoe Police.