Spencer was born in Montgomery, Alabama, the sixth of seven children. She attended Auburn University and has a bachelor's degree in liberal arts.

Spencer's first role was a bit part in the 1996 film A Time to Kill, based on the book by John Grisham. She also appeared briefly in the film Bad Santa as Opal, an associate of Willie Stokes, and in Spider-Man as the Check-In girl at the arena. Spencer most recently appeared as the Landlady in the 2006 horror film, Pulse. On television, Spencer has been featured in guest appearances on numerous shows. She is best known for three roles: the role of Serenity Johnson (of which she was a starring role) on the Comedy Central show Halfway Home, and for her recurring appearances as amorous Ex-INS caseworker Constance Grady on the dramedy series Ugly Betty, and a social worker in the third season of Titus.

Spencer is portraying the role of Dr. Evilini on the Disney series "Disney Wizards." (formerly "the Amazing O'malleys")