Lisa Ann was born in Easton, Pennsylvania. She began erotic dancing in 1991 to pay her way through college to become a certified dental assistant. In July 1993, she became an adult actress, but quit in 1997 due to an AIDS scare. She spent several years touring as a feature dancer at strip clubs around the country, before returning to the sex industry as an agent, and later also as a performer. Her first "comeback" movie was released on February 16, 2006.
Her talent agency, Clear Talent Management, formed in November 2006, was later renamed Lisa Ann's Talent Management and merged with Adam Glasser's Lighthouse Agency in 2007 and eventually closed in July 2010.
Lisa Ann as Serra Paylin at the AVN Expo, Las Vegas, Nevada on January 8, 2010
On October 2, 2008, Lisa Ann was confirmed to star in Who's Nailin' Paylin? parodying 2008 Republican Vice Presidential candidate Sarah Palin. The movie, produced by Larry Flynt'sHustler Video, portrays Lisa Ann in sex scenes with other female porn stars parodying well-known female political figures, such as Hillary Clinton (played by veteran porn star Nina Hartley) and Condoleezza Rice (played by Jada Fire). This movie was released on election day November 4, 2008. On October 31, 2008 Hustler announced that Lisa Ann was going to star in Obama is Nailin' Paylin a scene that continued the adventures of Lisa as Sarah Paylin except this time Barack Obama would be lampooned as well. The scene is only available through their Hustler members website and on the Blu-ray release of the movie. It is not available on the DVD release. This "bonus scene" was released on election eve November 3, 2008. On August 26, 2009 Hustler released "Letterman is Nailin Palin". She reprised her role as "Serra Paylin" in a cameo appearance in Eminem's music video "We Made You" where she was cast at the director Joseph Kahn's suggestion. These appearances revived her on-screen career.
In December 2009, it was announced that Lisa Ann had signed on to be the spokeswoman for RealTouch, a mechanised artificial vagina produced by AEBN. She later had her own genitalia molded for Fleshlight in 2011.
In August 2013, she launched her own production company, Lisa Ann Productions, and signed a distribution deal with Jules Jordan Video. Her directorial debut for the company, MILF Revolution, was released on August 5, 2013.
Lisa Ann is a recurring guest on The Howard Stern Show. Her first appearance on the show was as a "Snapple Girl", prior to the beginning of her adult entertainment career.
Lisa Ann was ranked fifth on Complex Magazine's list of "The Top 100 Hottest Porn Stars (Right Now)" in 2011. She was also placed on CNBC's yearly list "The Dirty Dozen: Porn's Most Popular Stars" in 2011 and 2012. In April 2013, New York Post reported that she was "the most popular female porn star" according to data provided by Pornhub.
Lisa Ann appeared in the 2013 documentary film Aroused alongside 15 other pornographic actresses.
In August 2013, Lisa Ann starred in the music video for the song "Dead Bite" by Hollywood Undead.