Mowry and her sister began entering pageants and talent shows while their family was stationed at Fort Hood, Texas. Mowry's mom Darlene removed the twins from the early 90s R&B girl group Voices after a disagreement with management prior to the release of their debut album. At age 12, they convinced their mother to move to California with them so they could pursue acting. She agreed on the condition that they land an acting job within the first month of their stay. In 1990, their family moved to California permanently, settling in Los Angeles, and she and her sister began appearing in commercials and small roles.

She is well known for playing Tia Landry, a twin separated at birth and reunited with her sister as a teenager in the show Sister, Sister. The series was developed for them after a producer spotted them on the set of Full House, a show on which their brother made regular appearances. Sister, Sister was initially on ABC but was cancelled by the network after two years and picked up by The WB, where it ran for another four years. During its run, they guest-starred on the Sister, Sister crossover episode of The Jamie Foxx Show and appeared on an episode of their brother Tahj Mowry's sitcom Smart Guy and did voice-over work for the Kids' WB series Detention.

After the show ended, both Mowry and her sister studied psychology at Pepperdine University. She also went to Europe to study humanities and Italian for a period. Both she and her sister appeared in the Rob Schneider comedy film The Hot Chick, playing cheerleaders. Mowry also did voice-overs for the 4KidsTV cartoon Bratz as the voice of Sasha. In 2005, Mowry and her sister both starred in the Disney Channel Original Movie Twitches and reprised their roles in its sequel, Twitches Too and before co-starred in the 2000 movie Seventeen Again. Tia also appeared on an episode of her sister's television show, Strong Medicine, in January 2006, playing the role of Keisha, the twin sister of Tamera Mowry's character, Dr. Kayla Thornton. Mowry has a starring role in the BET television series The Game as Melanie Barnett. Mowry has been nominated for a Teen Choice Award and an NAACP Image Award for best actress in a comedy.