Mathis began acting professionally at the age of 16. Her first job was a commercial for "
Always Slender Pads – Just for Teens".
Super Mario Bros. (1993), in which she played
Princess Daisy from the popular
Nintendo video game, was a
box-office bomb but gained a
cult following since its release. Mathis co-starred with
River Phoenix in
The Thing Called Love (1993). She appeared in the 1994 film adaptation of
Little Women, and in
How to Make an American Quilt (1995), both starring
Winona Ryder. She then appeared in
The American President (1995), playing the assistant to the
President of the United States. Mathis costarred with Christian Slater again, along with
John Travolta, in
John Woo's
Broken Arrow (1996). She took a little over a year off from acting after her mother died in 1996 from breast cancer. Her indie film
Lebanon, PA (2010) had its world premiere at the 2010
SXSW Film Festival. She appeared in an
off-Broadway production of the play,
Love, Loss, and What I Wore, at
New York City's
Westside Theatre in October 2011. In 2013, Mathis played psychiatrist Alice Calvert on the
CBS television series
Under the Dome, based on a novel by
Stephen King. In 2014, she joined the cast of the
FX horror drama series
The Strain as Justine Feraldo, a
New York City councilwoman for
Staten Island. In October 2015, Mathis was elected National Vice President, Actors/Performers of
SAG-AFTRA. She was re-elected in 2017. Her 2020 musical
Whisper House was postponed due to the
COVID-19 pandemic. ==Personal life==