Bledsoe earned a bachelor's degree in Finance from New York University. Since 1993 she has been in a relationship with actor Darryl M. Bell, who co-starred in the NBC TV comedy A Different World, a spinoff of The Cosby Show. The couple appeared together in the Fox Reality Channel series Househusbands of Hollywood, which debuted August 2009. Bledsoe is a vegetarian.

In 1984, Bledsoe was cast in the role of Vanessa Huxtable on the sitcom The Cosby Show. She was a regular until its final season in 1992. She also made a one-time appearance as Vanessa on A Different World. In 1986, Tempestt played the role of Grace Wheeler in Season 15, Episode 4 (The Gift Of Amazing Grace), of the ABC Afterschool Special program. In the mid-1990s, Bledsoe hosted a daytime talk show, The Tempestt Bledsoe Show, produced by Columbia-Tristar and Dick Clark. She made a brief appearance in the sitcom The Parkers, and has been featured in the recurring role of a single mother on the ABC show The Practice. She also appeared in the Lifetime show Strong Medicine, and South of Nowhere. Her most recent credits include the role of Nina in the Oxygen Channel's original television movie Husband for Hire, Steven Bochco's Raising the Bar, and the role of Abby in the third season of Disney Channel's animated series The Replacements. She appeared on VH1's Celebrity Fit Club. It was announced on December 1, 2010 that Bledsoe would return to TV, replacing Niecy Nash as the host of Clean House on Style Network. Her first episode aired on January 26, 2011. In 2012, Bledsoe was heard as the voice of Sheriff Hooper in the Laika animated film ParaNorman. In 2014, Bledsoe appeared in the Instant Mom episode "Not Your Mother's Day" in which she reprised her role as Vanessa Huxtable.