Lopes was born in 1971 in Philadelphia, Pennsylvania, the daughter of Wanda Denise (née Andino), a seamstress, and Ronald Lopes Sr., a US Army staff sergeant. Lisa had a younger brother, Ronald Jr., and a younger sister, Raina Anitra (nicknamed Reigndrop). Lopes said her father was “very strict, very domineering” and that he treated the family like they were in “boot camp”. He was also a “talented musician” who played the harmonica, clarinet, piano, and saxophone.

In late 1990, having heard of an open casting call for a new girl group through her then-boyfriend, Lopes moved to Atlanta to audition. Originally starting as a female trio called 2nd Nature, the group was renamed TLC, derived from the first initials of its members at the time: Tionne Watkins, Lisa Lopes and Crystal Jones. Things did not work out with Jones, and TLC’s manager Perri “Pebbles” Reid brought in Damian Dame backup dancer Rozonda Thomas as a third member of the group. To preserve the band’s original name, Thomas needed a name starting with C, which is how she became “Chilli,” a name chosen by Lopes. Watkins became T-Boz, derived from the first letter of her first name and “Boz” (slang for “boss”). Lopes was renamed “Left Eye” after a compliment from New Edition member Michael Bivins who once told her he was attracted to her because of her left eye, which was more slanted than the right eye. Lopes emphasized her nickname by wearing a pair of glasses with the right lens covered by a condom in keeping with the group’s support of safe sex, wearing a black stripe under her left eye, and eventually getting her left eyebrow pierced.

The group arrived on the music scene in 1992 with the album Ooooooohhh… On the TLC Tip. With four hit singles, it sold six million copies worldwide, leading to the group becoming a household name. Two years later, in 1994, Lopes began dating Atlanta Falcons American football player Andre Rison shortly after the release of Ooooooohhh… On the TLC Tip, the two were living together in Rison’s upscale double-story home. Their relationship was allegedly filled with violent moments, and Lopes filed an assault charge against Rison on September 2, 1993. Rison denied battering her. Lopes was also battling alcoholism at the time. She had been a heavy drinker since the age of fifteen. After another fight between the couple in the early morning hours of June 9, 1994, Lopes tossed numerous pairs of Rison’s newly purchased shoes into a bathtub, doused them with lighter fluid, and lit them on fire. The fiberglass bathtub quickly melted and set the structural frame of the house on fire. Lopes and Rison had a fight previously, because Rison had bought stuffed animals for another woman. Lopes doused them and lit them on fire, in which her and Rison had replaced it with the fiberglass tub. Lopes was arrested and indicted on charges of first-degree arson; she was sentenced to five years of probation and a $10,000 fine. Rison eventually reconciled with Lopes, and they continued dating on and off for seven years. Shortly after, CrazySexyCool was released, selling over 23 million copies worldwide. After the release of CrazySexyCool , Lopes was featured for the first time on How Do You Like It? a song by Keith Sweat in 1994. Later in 1995, Lopes was seen with TLC featured in Freedom (Rap Version) with other artists. In 1996, Lopes was featured on Gee, Officer Krupke with other artists like, Salt-n-Pepa, Def Jef etc. One year later, Lopes was featured on Lil’ Kim ‘s Not Tonight (remix) with other artists like, Da Brat, Missy Elliot, and Angie Martinez. After that she was featured on Will Smith‘s Big Willie Style. She was later featured on Donell Jones‘s U Know What’s Up, while in the middle of TLC’s third album, FanMail, which was released in 1999 and sold over 14 million copies worldwide. Lopes began working with her group Blaque in which the group ran under Left Eye Productions. Blaque was working on I Do (Blaque song). Its title was a tribute to TLC’s loyal fans and the sleeve contained the names of hundreds of them as a “thank you”.

Other tracks covered other personal issues, including her relationship with NFL football player Andre Rison. In 1994, before the start of Rison’s fifth and final season with the Falcons, Lopes accidentally burned down Rison Atlanta mansion. Among the album’s 13 tracks was also a posthumous duet with Tupac Shakur that was assembled from the large cache of unreleased recordings done prior to his murder in 1996. Initially scheduled for release on a date to coincide with the 11th anniversary of her grandfather’s death, Arista Records decided to delay and then cancel the American release. The album was eventually released in August 2001 in different foreign countries. The Japan import includes a bonus track called “Friends”, which would later be sampled for “Give It to Me While It’s Hot” on TLC’s fourth album 3D.

Lopes was often vocal about her personal life and difficult past. She openly stated that she came from an abusive, alcoholic background and struggled with alcoholism herself. These issues became headline news in 1994, when she was arrested for setting fire to Andre Rison’s sneakers in a bathtub, which ultimately spread to the mansion they shared and destroyed it. She claimed that Rison had beaten her after a night out, and she set fire to his shoes to get back at him but that burning down the house was an accident. Lopes later revealed that she did not have a lot of freedom within the relationship and that Rison abused her emotionally and physically; she said that she released her frustrations about the relationship on the night of the fire.

In 1996, Lopes created the UNI Studios for the purpose of recording solo projects. Lopes’ family opened the studio to the public. Her brother Ronald is the general manager of the studio. Lopes had a dream of making new artists able to record music at a low cost, in a high-end studio at her house. Her family continues to operate it and fill it with new equipment.

In 1998, Lopes hosted the short-lived MTV series, The Cut, in which a list of aspiring pop stars, rappers, and rock bands competed against each other in front of judges. The show’s winner, which ended up being a male-female rap duo named Silky, was promised a record deal and funding to produce a music video, which would then enter MTV’s heavy rotation. A then-unknown Anastacia finished in third place, but ended up securing a record deal after Lopes and the show’s three judges were impressed by her performance.

After the release of FanMail, Lopes began to expand her solo career. She also began to put aside everything negative. In 2000, Lopes and Rison’s rocky seven year relationship had stopped. Rison revealed on Lifetime’s “Hopelessly In Love,” that he and Lopes were engaged and was planning to get married in the early 2000. Due to Lopes’ death it was cancelled. Later on, She became a featured rapper on several singles, including Spice Girl Melanie C’s “Never Be the Same Again”, which topped the charts in 35 countries, including the United Kingdom. She was also featured on “U Know What’s Up”, the first single from Donell Jones’ second album, Where I Wanna Be, and she rapped a verse in “Space Cowboy” with NSYNC on their 2000 album, No Strings Attached. On October 4, 2000, Lopes co-hosted the UK’s MOBO Awards with Trevor Nelson, where she also performed “U Know What’s Up” with Jones. She also collaborated on “Gimme Some” by Toni Braxton for her 2000 album The Heat. She had previously featured on Keith Sweat’s song “How Do You Like It?”. In 2001, she appeared in a commercial for the fashion brand Gap. In July 2001, Lopes appeared on the singers’ edition of Who Wants to Be a Millionaire along with Joey McIntyre, Tyrese, Nick Lachey, and Lee Ann Womack. She dropped the $125,000 question and won $32,000 for her charity. After her death in 2002, the episode she appeared in was shown and was dedicated to her.

In September 2000, Lopes was reported missing after failing to attend a family gathering and a major press conference in Las Vegas.

After numerous talks with Death Row Records CEO Suge Knight, Lopes severed her solo deal with Arista (despite remaining signed to the label as a member of TLC) and signed with Knight’s Death Row Records in January 2002, intending to record a second solo album under the pseudonym “N.I.N.A.” (New Identity Not Applicable). She was recording with David Bowie for the project, whom she was also trying to get involved with the fourth TLC album. The project was also to include several songs recorded with Ray J along with close friend Missy Elliott. After Lopes’ death in April 2002, Death Row Records still had plans to complete and release the album (unfinished at the time of Lopes’ death) in October 2002, but the album was cancelled for unknown reasons. In 2011, some tracks from the album were uploaded onto YouTube featuring artists from Tha Row Records. Lopes’s unreleased songs were also sampled by TLC for their fourth album 3D after she died. Another track, “Too Street 4 T.V” (featuring Danny Boy), was released on the soundtrack to the 2003 film Dysfunktional Family.

On April 25, 2002, Lopes was driving a rented Mitsubishi Montero SUV in La Ceiba, Honduras, when she swerved slightly to avoid a truck (it is not clear if the truck was slow-moving or stationary) then immediately to the right as she tried to avoid an oncoming car. The vehicle rolled several times after hitting two trees, throwing Lopes and three others out of the windows, and finally coming to rest in a ditch at the side of the road. Lopes, at the age of 30, died instantly of “fracture of the base of the cranium” and “open cerebral trauma”, and was the only person fatally injured in the accident. A cameraman in the front passenger seat was videotaping at the time, so the last seconds leading up to the swerve that resulted in the fatal accident were recorded on video. Her sister Reigndrop Lopes was in the vehicle and survived the collision.

Lopes’ funeral was held at New Birth Missionary Baptist Church in Lithonia, Georgia, on May 2, 2002. Thousands of people attended. Engraved upon her casket were the lyrics to her portion of “Waterfalls”, stating “Dreams are hopeless aspirations, in hopes of coming true, believe in yourself, the rest is up to me and you.” Gospel duo Mary Mary sang their song “Shackles (Praise You)” at the funeral. Lopes was buried at Hillandale Memorial Gardens in Lithonia.

In 2003, shortly after Lopes’ death, her family started the Lisa Lopes Foundation, a charitable group dedicated to providing neglected and abandoned youth with the resources necessary to increase their quality of life. Her spiritual motto was the one used for her foundation: “Energy never dies… it just transforms.” Her foundation went into various underdeveloped villages and gave new clothes to poor children and their families. In August 2007, the foundation hosted a charity auction, selling items donated by celebrities. It raised approximately $5,000 for the Hogar de Amor (“Home of Love”), an orphanage in Honduras. In 2012, the foundation began hosting an annual music festival, known as “Left Eye Music Fest”, in Decatur, Georgia. In the 2018 Boots Riley film Sorry to Bother You, members of a fictional activist group called “Left Eye” use as their symbol a stripe of eye black under the left eye, in an unmentioned reference to Lopes.

A documentary showing the final 27 days of Lopes’ life, titled The Last Days of Left Eye, premiered at the Atlanta Film Festival in April 2007, for an audience that included many of Lopes’ contemporaries, including Monica, Ronnie DeVoe, 112, Big Boi, India.Arie, and Cee Lo Green. VH1 and VH1 Soul broadcast the documentary on May 19, 2007. Most of the footage was shot with a handheld camera, often in the form of diary entries filmed by Lopes while on a 30-day spiritual retreat in Honduras with sister Reigndrop, brother Ronald and members of the R&B group Egypt. In these entries, she reflected on her personal life and career. A calmer side of her personality was on display, showing interests in numerology and yoga. In January 2020, Lifetime aired an episode of Hopelessly In Love, a docuseries that captures the relationships of the rich and famous, about Lopes and Rison’s tumultuous relationship. It showcased the complexity of their relationship and how she ended up with a felony arson charge for burning down Rison’s Atlanta mansion.

In 2008, Lopes’ family decided to work with producers at Surefire Music Group to create a posthumous album in her honor, Eye Legacy. Originally set to be released October 28, 2008, the release date was pushed back to November 11, then to January 27, 2009. The song ‘Neva Will Eye Eva’ and “Crank It”, both feature and were co-produced by Lopes’ sister Raina “Reigndrop” Lopes. The first official single from the album, “Let’s Just Do It”, was released on January 13, 2009 and features Missy Elliott and TLC. The second official single, “Block Party”, features Lil Mama. The album largely consists of reworked versions of tracks from the Supernova album. In November 2009, Forever… The EP was released which contained international bonus tracks not used on the Eye Legacy album. The EP was only available to download. An unreleased track featuring Lopes was uploaded to SoundCloud on the eve of the 10-year anniversary of her death by Block Starz Music.