Sedgwick made her debut at the age of 16 on the television soap opera Another World as Julia Shearer, troubled granddaughter of Liz Matthews. In 1988, she made a strong impression in a TV version of Lanford Wilson's Lemon Sky. During the 1990s, she appeared in several Hollywood movies, including Singles (1992), Heart and Souls (1993), Something to Talk About (1995), and Phenomenon, in which she played the love interest of John Travolta's character. She starred in the Emmy Award–winning 1992 made-for-TV film Miss Rose White as a Jewish immigrant who comes to terms with her ethnicity. She played the parts of Mae Coleman in 2003's Secondhand Lions and Stella Peck in the 2007 film The Game Plan. She also starred alongside her husband Kevin Bacon in the 2004 film The Woodsman. She dubbed the voice of Batwoman in the animated movie Batman: Mystery of the Batwoman.
Sedgwick married actor Kevin Bacon on September 4, 1988. Sedgwick learned in 2012, via her appearance on the U.S. TV show Finding Your Roots with Henry Louis Gates, that she and Bacon are tenth cousins, once removed.