The FBI has rescued 105 young people and arrested 150 alleged pimps in a three-day sweep in 76 US cities.
The agency, which described child prostitution as a "persistent threat", said it had been monitoring Backpage.com and other websites as a prominent online marketplace for sex for sale.
Backpage.com said that it was "very, very pleased" by the raids and that if the website were shut down to the advertisements, the ads would be pushed to sites that would not co-operate with law enforcement. The young people in the round-up, almost all of them girls, were aged 13 to 17.
The largest numbers of children rescued in the weekend initiative, Operation Cross Country, were in the San Francisco Bay and Detroit areas, along with Milwaukee, Denver and New Orleans.
The operation was conducted under the FBI's decade-long Innocence Lost National Initiative. The latest rescues and arrests were the largest such action to date.
"Child prostitution remains a persistent threat to children across the country," Ron Hosko, assistant director of the bureau's criminal investigative division, said. "We're trying to put this spotlight on pimps and those who would exploit."
In Operation Cross Country, government, state and local authorities co-operated in an intelligence effort aimed at identifying pimps and their young victims. The FBI said the campaign has resulted in rescuing 2,700 children since 2003. The investigations and convictions of 1,350 individuals have led to life imprisonment for 10 pimps.
In their efforts to identify child victims, investigators seek help wherever they can find it - in some cases from adult prostitutes, Mr Hosko said. He said almost all the victims in sweeps were girls and that the profiles of the victims cut across racial lines.
Social media is a common denominator in many of the rescues.
Last year five members of the Underground Gangster Crips contacted teenagers at school or through Facebook, DateHookUp.com or other online social networking sites, enticing the girls to use their looks to earn money through prostitution.