She entered the adult film industry in 2006 at the age of around 20 and has appeared in over 300 movies. According to The Root, she is known as the "Halle Berry of the porn industry" because of her crossover appeal. Stone stated in a 2014 interview that she "fell into" working in the adult film industry, but later chose to make a career of it because she wanted to be the best at what she was doing. She also tried a variety of looks early on in her career to create a unique appeal for her audience. She describes the look that she chose as "afro-centric '70s" and inspired by Actress Pam Grier.

Stone voted for Barack Obama in the 2008 United States presidential election and has voiced her support for Hillary Clinton in the 2016 United States presidential election.

Stone has stated that she enjoys acting, but did not have the opportunity to indulge it until she was cast as Denise Huxtable in the 2009 parody Not the Cosbys XXX. She went on to star in the 2011 Hustler’s Untrue Hollywood Stories: Oprah parody as the title character of Oprah Winfrey and in 2013 as Mel B (a.k.a. Scary Spice) in the Spice Girls parody OMG... It's the Spice Girls XXX Parody.

In 2013 she launched her own production company, Misty Stone Productions. She also produces and sells a line of organic beauty products that include a body butter candle. Her body has also been molded for the creation of a line of sex toys. Stone is the first African-American performer to be molded by the company that manufactures the Fleshlight.

Stone is a Los Angeles native, stating that she was "born and raised" in Inglewood, but spent some time living in Omaha, Nebraska. She states in a 2014 interview that she was "not sexually open" when she was younger and considered herself a tomboy. Stone played basketball in high school.