A task force involving local San Diego police, federal officers and naval intelligence arrested 14 people who were attempting to buy sex at the giant pop culture gathering.
Ten victims were rescued, nine of them adults, said California Attorney General Rob Bonta.
"Unfortunately, sex traffickers capitalize on large scale events such as Comic-Con to exploit their victims for profit," said Bonta, in a statement.
San Diego Comic-Con is one of the world's largest pop culture events.
Some 135,000 people were expected to attend the convention, which lasted from Thursday to Sunday.
Originally a grassroots event for comic books fans to meet, it has grown exponentially and is today used by giant Hollywood studios and A-list stars to launch their latest blockbuster movies and TV shows.
Christopher Davis, acting special agent in charge of Homeland Security Investigations in San Diego, said "highly attended events" like Comic-Con are often seen by criminals as "an opportunity to prey upon minors."
"Working together, teams identified and arrested more than a dozen individuals participating in these illegal acts in our city over the weekend," said San Diego Police Chief Scott Wahl.
Law enforcement personnel placed undercover advertisements soliciting sex in order to arrest sex buyers.
