Ann was born and raised in Easton, Pennsylvania. She entered the adult film industry in 1994. Her first scene was in Cinesex 2. During the first two years of her adult film career, she was under contract with Metro/Cal Vista and shot only once a month. She quit porn in 1997 due to an AIDS scare in the industry and spent the following seven years stripping. She also owned a day spa for four years during her hiatus from porn. She decided to resume performing in February 2006 after being asked to do a boy/girl photo shoot for Suze Randall. The first scene she shot after returning to the industry was with Christian XXX in Bra Bustin' and Deep Thrustin'. In addition to her work as a performer, she also has credits as a director, producer, and for makeup.
She was selected to co-host the XRCO Awards in April 2010. In December 2014, she announced her retirement from performing in adult films in a Facebook post. She had a breast reduction surgery shortly after retiring as part of her return to a normal life. She continues to perform in webcam shows occasionally.
In 2008, Ann starred as "Serra Paylin," a parody of Republican vice presidential nominee Sarah Palin, in Hustler Video's Who's Nailin' Paylin?, which was released on Election Day. Hustler contacted Ann to offer her the part on the day of the vice-presidential debate, which she viewed to learn Palin's mannerisms in preparation for the role. She also prepared for the role by studying Tina Fey's impressions of Palin. She portrayed Palin again for the sequels Obama Is Nailin' Palin, Letterman's Nailin' Palin, You're Nailin' Palin, Hollywood's Nailin' Palin, and Who's Nailin' Palin? 2. Hustler also produced a mask in the likeness of Ann portraying Palin for Halloween in 2009. Ann reprised her role as Palin in the music video for the song "We Made You" by Eminem. She has also performed as Palin at strip clubs. These appearances revived her on-screen career.
Lisa Ann made her directorial debut with the film, Hung XXX, released on September 22, 2009 by Justin Slayer International. 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. MILF Revolution won the 2014 AVN Award for "Best MILF Release".
Ann worked as a talent agent for LA Direct Models between September 2005 and February 2006. According to Ann, female performers in the industry who were 30 years or older were rejected by other agents and had to represent themselves despite the demand for them amid the "MILF phenomenon," which motivated her to start her own agency and represent them. She launched Clear Talent Management in November 2006, which was later renamed Lisa Ann's Talent Management and merged with Adam Glasser's Lighthouse Agency in 2007 before closing in July 2010.
In December 2009, it was announced that Lisa Ann had signed on to be the spokeswoman for RealTouch, a mechanized artificial vagina produced by AEBN. She later had her own genitalia molded for Fleshlight in 2011.
In 2013, Ann hosted a show titled Stripper Town on Sirius XM. She currently co-hosts Lisa Ann Does Fantasy, alongside Adam Ronis, on Monday nights and The Morning Men on Thursday mornings, both on Sirius XM Radio. In December 2014, she stated that she is pursuing a career in fantasy football. By January 2016, she was slowly getting involved with fantasy baseball as well.
On December 15, 2015, Ann released a memoir titled The Life.
In August 2014, Lisa Ann reached out to fellow porn actress Belle Knox, also known as the "Duke [University] porn star". Through her agent, who also represents Knox, she wanted to see "How's she doing?". Lisa Ann has been mentoring an average of 10 to 15 girls since 2005. In an interview conducted by XBIZ Lisa Ann said she could sympathize with the media attention that Knox had faced. She experienced a similar one in 2008 when she played former vice presidential candidate, Sarah Palin. "I understand that being a new girl in the business can be a very lonely place... She's already out on the road feature dancing, already has a million opportunities and I feel like if that all happened to me, if 'Palin' had happened to me at 19, I don't know how I would've managed it," stated Lisa Ann. "So I reached out to her and we started just a little bit of mentoring by text, by phone, by Skype. And I enjoyed the bond when we talked." In December 2014, she launched Porn Stars Boot Camp, a consulting firm.
Lisa Ann appeared on The Howard Stern Show as a "Snapple Girl", prior to the beginning of her adult entertainment career.
On November 7, 2008, Ann appeared on Entertainment Tonight to promote Who's Nailin' Paylin?.
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, 2012, 2014, and 2015. In April 2013, New York Post reported that she was "the most popular female porn star" according to data provided by Pornhub.
Ann was among the sixteen pornographic actresses profiled in the 2013 documentary film Aroused. In August 2013, she starred in the music video for the song "Dead Bite" by Hollywood Undead. She voiced a character known as "Prostitute #2" in the video game Grand Theft Auto V, released in September 2013.
Ann does not identify with any political party. In October 2008, she said she was voting for Barack Obama in the 2008 presidential election and that she was previously a supporter of Hillary Clinton. She supported Obama again in the 2012 presidential election. Ann has expressed support for gun rights.
In March 2010, Lisa Ann appeared in a Public Service Announcement for the Free Speech Coalition on the topic of copyright infringement of adult content, directed by Michael Whiteacre.
On October 14, 2010, Ann announced that she would only be shooting scenes with condoms after a male performer in the industry was diagnosed with HIV. She also stated that the STD testing system at the time wasn't enough and encouraged other performers to demand condom use during shoots as well. In August 2012, she called for legislation mandating condom use in heterosexual adult films and questioned the standards of syphilis treatment for performers by industry doctors. In August 2013, she alleged that a male performer she was scheduled to work with may have tested positive for hepatitis C and tried to work anyway. She stated that the performer showed her a test from a facility outside of the industry which did not indicate any results for hepatitis and that she discovered two adult performer testing databases had him listed as unavailable to work. Subsequently, the Adult Production Health & Safety Services announced that they would start implementing monthly hepatitis B, hepatitis C, and trichomoniasis testing on August 19, 2013. While in the industry, she paid for a fresh round of tests for her co-stars to ensure they were clean.
Ann has campaigned to destigmatize interracial pornography by speaking out about the treatment of black performers in the industry and the lack of work for them. She also wants to help transform the industry to give performers pensions, health insurance, and career guidance.
Ann lived in Huntington Beach, California for at least fifteen years. She once lived in Boca Raton, Florida for a year as well. As of October 2015, she owns a condo in Los Angeles and an apartment in Midtown Manhattan. She is a sports fan, her favorite sports being basketball and football. In high school, she played basketball and was in the ski club. She stated that if she hadn't worked in the adult film industry, she would have liked to become a sports agent or writer, blogger, and reporter. She is a fan of the Los Angeles Lakers and the Dallas Cowboys. At age 28, Ann married a bouncer, whom she later divorced. In November 2009, she told TMZ that she started dating Rob Kardashian after meeting him at a gym. A source close to Kardashian spoke to Us Weekly and confirmed that they met at a gym, but denied Ann's claim that they were dating. Due to her interest in sports and professional athletes along with her work as a sports reporter for the Sirius/XM network, Lisa Ann attends numerous games, which has led to interaction, sometimes publicly, with athletes. In October 2014, speculation was raised whether Lisa Ann and 18-year-old Notre Dame football player Justin Brent were dating when the two appeared at a game together. After their appearance at Madison Square Garden, personal photos of the two in bed together were then released online. In November 2014, Lisa Ann commented via her Twitter account regarding requests made to her by former New York Rangers hockey player Michael Del Zotto.
In a February 2014 interview with GQ magazine sports writer Myles Brown, Lisa Ann stated "...if dudes could be with Victoria's Secret models, that's how I look at athletes. I'm 42. I'm looking at 18, 19, 20-year-old guys." and continued, "They're at the beginning of their lives, so they're still excited, naive and simple. They're not negative yet." When asked how many athletes she had slept with, she replied, "In my life in the [adult] business for twenty-something years? A lot. Hundreds." She later stated in the interview that her preference of athlete to interact with or have a relationship is NBA players. Lisa Ann stated that this can lead to awkward situations, for example, when players are traded and several athletes she is in contact with are on the same team, a situation she makes the effort to avoid. "I don't mess with multiple guys on a team at the same time. I don't want to be in any locker room talk."
In March 2015, during the annual March Madness NCAA basketball tournament, there was media attention regarding a promotion she promoted in conjunction with the production studio Brazzers. The contest, "Win a Date with Lisa Ann", was co-sponsored by the studio and offered an all-expense-paid trip to the national championship game for the best trick shot video submitted. Unexpectedly, Brazzers withdrew the promotion via press release effectively shutting down the contest.