Sonny Szeto, 22, of New York, used the site to meet an 11-year-old girl, while Stephen Letavec, 39, of Pennsylvania used it to meet a 14-year-old girl, federal authorities said.
"People with nefarious intentions exploit that technology and target our children," Kevin O'Connor, U.S. Attorney for Connecticut, said at a news conference in New Haven, Connecticut.
Some 60 million users post photographs and personal information about themselves on the social-networking site owned by Rupert Murdoch's News Corp.
MySpace Chief Executive Chris DeWolfe declined to comment on the arrests, saying the company doesn't discuss criminal investigations.
He said MySpace has several measures in place to prevent abuse: It prohibits children under age 14 from using the site; It also restricts access to the profiles of 14- and 15-year-olds, allowing them to be contacted only by users that they add to their buddy lists.
MySpace also uses software to identify minors, flagging profiles with terms likely to be used by children under age 14. Some 200,000 profiles have been deleted from the site on suspicion that users had lied about their age.
Still, there's no fool-proof way for MySpace or any other Internet site to verify the age of all users, DeWolfe said in an interview.
In a bid to fight abuse, the company posts warnings about the potential for its members to become crime victims. "We think that education is the most important piece," he said.
O'Connor said the blame doesn't lie with MySpace. "This really is about the predators," the U.S. attorney said in an interview. "When it comes to blame you can only point the finger at the defendants."
Szeto and his victim also chatted over Time Warner's AOL Instant Messenger service, viewed Webcam images of each other and spoke over the telephone, according to court documents.
He arranged three late-night visits to her home in Connecticut, where they had sexual contact, according to an FBI affidavit. Szeto was arrested on Feb. 27.
Letavec is accused of using MySpace to arrange meetings with a 14-year-old girl, also in Connecticut, where they had sexual contact, according to the court documents.
Representatives for AOL were not immediately available for comment.
Neither Szeto nor Letavec has been indicted.
Letavec faces possible charges of using the Internet to persuade a minor to engage in sexual activity and with traveling in interstate commerce for the purpose of attempting to have and having illicit sexual conduct with a minor. If convicted, he faces a maximum of 60 years in prison.
Szeto faces charges of using the Internet to persuade a minor to engage in sexual activity. If convicted, Szeto could face 30 years in prison.