Lopes, who would have turned 31 next month, was driving in the Central America nation when the accident happened Thursday night, spokesman Jay Marose said Friday. He said she had a condo there and visited frequently.
Seven other people, including Lopes' brother and sister, were in the Mitsubishi Montero sports utility vehicle when the crash happened near Jutiapa, 150 miles north of Tegucigalpa, the Honduran capital.
"The car rolled for reasons that we still don't know, and that are being investigated," police spokesman Luis Aguilar said. Lopes was killed instantly; several other people in the car were taken to a hospital for injuries that were not life-threatening.
TLC, which also includes Tionne "T-Boz" Watkins and Rozonda "Chilli" Thomas, had such hits as "Waterfalls," "No Scrubs" and "Unpretty." Their latest album was "FanMail."
The Atlanta-based R&B group is the best-selling female group in history in terms of album sales, having sold 21 million. The Supremes are the top all-female group in terms of No. 1 hits, garnering 12 compared with TLC's four.
Watkins and Thomas said they were devastated by the death. The group had recently been working on the follow-up to their Grammy-winning, triple-platinum disc "Fanmail," released in 1999.
"We are sisters, we had been together for more than 10 years," Watkins said Friday in a tearful phone interview with MTV's "Total Request Live."
Their songs delivered a message of female empowerment, using sassy, tongue-in-cheek rhymes. The lyrics to "Ain't Too Proud to Beg," "Waterfalls," and "No Scrubs" were straight from the streets yet poignantly addressed safe sex, AIDS, black on black crime and self-respect.
The group made its debut in 1992 with the disc "Ooooooh ... On the TLC Tip!" Their unique sound, which paired Watkins and Thomas' vocals with Philadelphia-born Lopes' fast-paced, squeaky-voiced rhymes, along with their baggy wardrobe with condoms attached, made them an immediate sensation.
Lopes' nickname came from her habit of replacing one lens of her glasses with a condom during performances.
In 1994, the band returned with "CrazySexyCool" — Lopes was dubbed the "crazy" member of the group, Thomas the "sexy" one and Watkins the "cool" one. The quadruple platinum album saw the women abandon their sometimes gimmicky image to evolve into a critically acclaimed group. The disc included the No. 1 hit "Creep" and won them the first two of their four Grammy Awards.
The band also soon became know for its flashy, hyper videos and picked up a clutch of MTV Video awards. Lopes even was a host for MTV's daily show, "The Cut."
Lopes delivered her lines with authority.
"No words can possibly express the sorrow and sadness I feel for this most devastating loss," said Arista president L.A. Reid, who helped shape TLC's career.
"No Scrubs," written by members of another Atlanta group, Xscape, drew attention for its take on underachieving men with overactive egos. "I'm looking like class and he's looking like trash," it says.
It even inspired an answer song from the hip-hop group Sporty Thievz, "No Pigeons," which took aim at gold-digging women. "You birds wanna take over?" it says. "Get some cash and a Jenny Jones makeover."
But with success came enough turmoil to fill a VH1 "Behind the Music" special. The trio declared bankruptcy a few years ago, citing poorly structured recording contracts. Watkins was hospitalized several times, suffering from sickle cell anemia.
In 1994, Lopes pleaded guilty to arson in a fire that destroyed the million-dollar mansion of her boyfriend, former Atlanta Falcons receiver Andre Rison. Lopes was sentenced to a halfway house and five years' probation, plus a $10,000 fine.
Lopes admitted she started the fire after an argument with Rison. The two later broke up, only to reunite and break up again. However, last year they announced plans to marry.
Infighting among group members also was reported. In 2000, after the release of the triple-platinum disc "FanMail," Lopes challenged Watkins and Thomas to put out solo albums, and let fans determine who was the most popular group member. But her own solo album, "Supernova," was shelved last year when radio stations showed little interest.
In an interview with The Associated Press last year, Watkins dismissed talk of a rift.
"With three women, you agree to disagree. I'm not always going to agree with Lisa and she's not always going to agree with me," she said. "That's fine."
TLC had been on hiatus, but had recently been in the studio working on a new record due to have been released this year.
In the past few months, Lopes reportedly signed a solo deal with Suge Knight's Tha Row label to put out another solo project under the pseudonym, "N.I.N.A." (New Identity Not Applicable). She also helped start the group "Blaque," an R&B trio who had the hit "Bring It Home To Me."
For years, Lopes would escape to her condo on Honduras' northern coast, attending a nearby healing village and returning "spiritually cleansed," Marose said. The village promotes and practices a form of African herbal medicine, he said.
She also was working on a line of clothing and a book, he said.
Lopes' manager flew to Honduras to bring her body home, her record label said. She is survived by her mother, and her younger brother and sister.