Jenna Marie Massoli was born in Las Vegas, Nevada. Her father, Laurence Henry Massoli, was a Police officer at the Las Vegas Sheriff's Department and program Director for KSNV-DT. Her mother, Judith Brooke Hunt, was a Las Vegas showgirl who danced in the Folies Bergère show at the Tropicana Resort & Casino. Her mother died of melanoma on February 20, 1976, two months before her daughter's second birthday. The cancer treatments bankrupted the family and they relocated in Nevada, Arizona and Montana, usually living in a trailer home or with her paternal grandmother. She and her older brother Tony were raised Catholic, though they were essentially left to parent each other.

Jameson wrote in her autobiography that in October 1990, when she was 16 years old and while the family was living on a cattle ranch in Fromberg, Montana, she was beaten with rocks and gang raped by four boys after a football game at Fromberg High School. The incident began after she attempted to hitchhike home and that she entered the car of the four boys while believing that she would be driven to her home. She reported being raped a second time while still 16 by "Preacher", her boyfriend Jack's biker uncle. Preacher has denied the rape ever occurred. Rather than tell her father, she left home and moved in with Jack in her first serious relationship.

Besides dancing, starting later in 1991, she posed for nude photographs for Photographer Suze Randall in Los Angeles, with the intention of getting into Penthouse. After her photos had appeared in several men's magazines under various names, she then stopped working for Randall, feeling Randall was "a shark".

Jameson says that she started acting in sex videos in retaliation for the infidelity of her boyfriend, Jack. She first appeared in an erotic film in 1993, a non-explicit softcore movie by Andrew Blake, with girlfriend Nikki Tyler. Her first pornographic movie scenes were filmed by Randy West and appeared in 1994's Up and Cummers 10 and Up and Cummers 11. She quickly achieved notice and appeared in several other pornographic films while still living in Las Vegas.

In 1994, after overcoming her drug addiction by spending several weeks with her father and grandmother, Jameson relocated to Los Angeles to live with Nikki Tyler. Her first movie after that was Silk Stockings. Later in 1995, Wicked Pictures, a then small pornographic film production company, signed her to an exclusive contract. She remembers telling Wicked Pictures founder Steve Orenstein: "The most important thing to me right now is to become the biggest star the industry has ever seen."

The contract earned Jameson US$6,000 for each of eight movies in her first year. Her first big-budget production was Blue Movie (1995), where she played a reporter investigating a porn set; it won multiple AVN Awards. In 1996, Jameson won top awards from three major industry organizations, the XRCO Best New Starlet award, the AVN Best New Starlet Award, and the Fans of X-Rated Entertainment (F.O.X.E.) Video Vixen award. She was the first entertainer to win all three awards. A stream of other awards followed.

On December 20, 1996, Jameson married porn star/Wicked Pictures Director Brad Armstrong (real name Rodney Hopkins). The marriage lasted just 10 weeks. Although they informally separated in March 1997, she remained contractually obligated to work on Wicked Pictures projects involving both of them. They legally separated and divorced in March 2001, after Brad discovered her sexual affair with Jorge Araya Montoya (whom she met on a visit to Costa Rica).

Jameson has also crossed over into mainstream pop culture, starting with a minor role in Howard Stern's 1997 film Private Parts. Her mainstream appearances continued with several guest-hosting and guest-starring on various television programs. Playboy TV hosted her Jenna's American Sex Star reality show, in which aspiring porn stars competed for a ClubJenna contract. Her 2004 autobiography, How to Make Love Like a Porn Star: A Cautionary Tale, spent six weeks on The New York Times Best Seller list.

In 1995, Jameson sent photos of herself to radio host Howard Stern. She became a regular guest on his show, appearing more than 30 times, and played the role of "Mandy", the "First Nude Woman on Radio", in Stern's semi-autobiographical 1997 film Private Parts. This film appearance was the beginning of a series of non-porn film and television roles. In 1997, Jameson made an appearance for an Extreme Championship Wrestling pay-per-view, Hardcore Heaven '97 as the valet for The Dudley Boyz; another appearance at ECW Living Dangerously on March 1, 1998; and a few months where she was ECW's on-screen interviewer. In 1998, she filmed a vignette with Val Venis, a character in the WWE, for airing on WWE programming. In the late 1990s, Jameson guest hosted several episodes of the E! cable network's hit travel/adventure/party show Wild On!, appearing scantily clad in tropical locations. Jameson was featured and interviewed on the British television show "European Blue Review" on Channel 5.

Some of her mainstream appearances sparked controversy. An interview with Jameson contained in the 1999 Abercrombie & Fitch A&F Quarterly was part of the motivation for Michigan Attorney General Jennifer Granholm and Illinois Lieutenant Governor Corinne Wood to speak out against the Hybrid magazine-catalog. The campaign was joined by parents and Christian conservative groups, and got the Quarterly removed from shelves and eventually canceled in 2003.

Jameson and Grdina formed ClubJenna as an Internet pornography company in 2000. ClubJenna.com was one of the first pornographic sites to provide more than pictures and videos; it provided explicit diaries, relationship advice, and even stock tips to paid members. The site reportedly was profitable in its third week. The Business later Diversified into multimedia pornographic entertainment, first by administering other porn stars' websites, then, in 2001, by production of pornographic films.

In November 2001, the Oxford Union debating society invited Jameson to come to Oxford to argue against the proposition "The House Believes that Porn is Harmful." She wrote in her diary at the time, "I feel like I am going to be out of my element, but, I could never pass this chance up ... it's a once in a lifetime thing." In the end, her side won the debate 204 to 27.

Jameson was featured prominently in Samhain, a low budget horror film in which she starred with other pornographic actresses including Ginger Lynn Allen. It was filmed in 2002 but had sat unreleased until 2005, when it was re-cut and released as Evil Breed: The Legend of Samhain. She had another minor horror film role in Sin-Jin Smyth, delayed from release until late 2006.

Jameson met former pornographic studio owner Jay Grdina (born John G. Grdina), scion of a wealthy cattle-ranching family, who had entered pornographic film production after college. From 1998 until Jameson's retirement, Grdina was Jameson's only on-screen male sex partner, acting under the name Justin Sterling. They were engaged in December 2000, well before her divorce from Armstrong/Hopkins, and married June 22, 2003. They tried to have children from mid-2004 onwards, as Jameson had planned to retire from adult entertainment upon becoming a mother. The couple resided in Scottsdale, Arizona, in a 6,700-square-foot (620 m) Spanish-style mansion, bought for $2 million in 2002.

In November 2004, Jameson was diagnosed with skin cancer. Though surgery removed it, she miscarried shortly after the diagnosis. She was unable to conceive again with Grdina, even with in vitro fertilization. Jameson said the in vitro process "wasn't a good thing for me"; she gained weight and did not get pregnant. According to Jameson, the stresses of the cancer plus infertility led to her marriage's collapse. In August 2006, Star magazine and TMZ.com confirmed with Jameson's publicist that she and Grdina had separated.

In August 2005, ClubJenna launched Club Thrust, an interactive website for Jameson's gay male fans, which includes videos, galleries, sex advice, gossip, and downloads. The Director of webmaster relations for ClubJenna said the straight site had always had a lot of gay traffic. By 2006, ClubJenna administered more than 150 official sites for other adult-entertainment industry stars.

In October 2006, it was reported that Jameson began dating mixed martial Artist and former UFC champion Tito Ortiz, whom she met on Myspace. Ortiz canceled a November 12, 2006 appearance as the guest of honor at the United States Marine Corps birthday ball at the Marine Corps Air Station Miramar in San Diego, when the Corps refused to let him bring Jameson as his guest. On November 30, 2006, in an interview on The Howard Stern Show, Ortiz stated that he was in love with Jameson, that she was no longer acting in pornography, and that they were in a monogamous relationship. On December 12, 2006, Jameson filed for divorce from Grdina. She introduced Ortiz and talked about their relationship at the 2008 AVN Adult Movie Awards while she was presenting an award. She also made brief appearances on two episodes of The Celebrity Apprentice to help Ortiz on the tasks assigned in those episodes.

In February 2006, Comedy Central announced plans to feature Jameson as "P-Whip", in a starring role in its first animated mobile phone series, Samurai Love God. Mediaweek called her the biggest name attached to the project. In April 2006, Jameson was the star of a video podcast ad for Adidas, advertising Adicolor shoes by playing a provocative game of whack a mole. In July 2006, Jameson became the first pornographic Actress to have a wax model at Madame Tussauds (in the Las Vegas museum). Jameson made an appearance in the U.S. reality TV show The Simple Life in the fifth-season episode "Committed", broadcast on July 1, 2007; Paris Hilton and Nicole Richie, while working in a "love camp", brought her in to help throw a "love ceremony" vow for the five dysfunctional couples. In 2008, Jameson had another starring role in the comedy horror film Zombie Strippers, loosely based on Eugène Ionesco's classic play Rhinoceros.

Jameson supported Democrat Hillary Clinton in the 2008 United States presidential election, but Republican Mitt Romney in the 2012 United States presidential election, stating: "I'm very looking forward to a Republican being back in office. When you're rich, you want a Republican in office." In late November 2015, Jenna made multiple tweets showing support for Donald Trump as the next President of the United States.

Jameson announced in August 2008 that she and Ortiz were expecting twins in April 2009. On March 16, 2009, Jameson gave birth to twin boys, Jesse Jameson and Journey Jette. Jameson and Ortiz split up in March 2013. Ortiz was granted full custody of the twins.

On April 26, 2010, Jameson's then husband, Tito Ortiz was arrested for felony domestic abuse at the couple's Huntington Beach, California home. Jameson was photographed afterward that day with a bandaged arm, amid accusations by both parties against each other, with Ortiz accusing Jameson of being erratic and addicted to OxyContin, while she alleged that he was abusive. Since the incident occurred, both parties have recanted these allegations that were made toward one another, though as of April 29, 2010, the investigation by the police department remained open.

On May 25, 2012, Jameson was arrested in Westminster, California and charged with three misdemeanor counts for driving under the influence of alcohol or other drugs, driving with a blood-alcohol level over the state legal limit, and driving on a suspended license after her Range Rover struck a light pole. She initially pleaded not guilty to the charges, but later changed her plea to guilty. She was sentenced to three years of informal probation, ordered to pay $340 in fines, and participate in a Mothers Against Drunk Driving victims' impact panel. The charge for driving without a valid license was dismissed.

Jameson is also known for achieving a high level of Celebrity outside of pornography – even bringing pornography itself closer to mainstream society's awareness and acceptance. She has said: "I've always embraced my hard-core roots, but becoming a household name was an important thing to me."

As of 2014, Jameson has undergone extensive tattooing, almost completely covering both of her arms in sleeve tattoos. In 2013, self-proclaimed socialite and Writer Britney Markham became Jameson's personal assistant after having met on Twitter. In a 2014 interview with LA Weekly, Markham claimed that Jameson would make requests for drugs. Markham posited that the pills of choice were Xanax, Ambien and Suboxone along with alcohol. At the same time, Markham denied that Jameson had been taking Oxycodone, in spite of previous rumors. Markham stated that she was assaulted and battered by Jameson following an incident in a hair salon in Los Angeles in 2013 when Jameson punched Markham in the stomach with a brass knuckles iPhone case. The blow was so severe, Markham claims she vomited blood and was hospitalized.

On August 27, 2015, Jameson became a contestant on the sixteenth series of the UK reality series Celebrity Big Brother, representing the USA. On September 22, she became the sixth housemate to be evicted on Day 27, just two days short from the final.

On November 11, 2016, Jameson announced on her Twitter feed that she completed her conversion to Orthodox Judaism with a Haredi rabbinical court in Upstate New York. Having been raised Catholic, in June 2015, Jameson announced that she was converting to Judaism, in order to marry Bitton. In October, an Israel Channel 2 reality television series was announced, which would document Jameson's conversion.

In 2017, Jameson criticized Playboy for featuring its first transgender Playmate for November 2017 Playmate.