Newsome began having an interest in acting as a child performing in community theater, before moving to New York City. While in New York, she was cast in a number of Broadway productions. She made her big screen debut appearing in a supporting role in the 1992 comedy film Straight Talk starring Dolly Parton. She went on to guest star in a number of notable television series, include Chicago Hope, Law & Order, Ally McBeal, Dharma & Greg, NYPD Blue, ER, Heroes, and Criminal Minds.

Newsome was regular cast member in a number of short-lived television series. First, she co-starred alongside Mark Feuerstein and Lauren Graham in the NBC sitcom Conrad Bloom (1998). In 2003, she appeared in the NBC legal drama The Lyon's Den starring Rob Lowe. From 2007 to 2008, she starred alongsode Angie Harmon, Laura Harris and Aubrey Dollar in the ABC police drama Women's Murder Club playing medical examiner Claire Washburn. The following years, she returned to playing guest-starring roles, appearing on The New Adventures of Old Christine, Bones, Parenthood, FlashForward, Drop Dead Diva, Grey's Anatomy, Suits, Castle, and most notable How to Get Away with Murder opposite Viola Davis, for which she received positive reviews. She also had the recurring roles on City of Angels, NCIS, and Suburgatory.

In film, Newsome has appeared in Guess Who (2005), Little Miss Sunshine (2006), Reign Over Me (2007), Things We Lost in the Fire (2007), Thinspiration and Black or White (2014).